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shp2 inhibitor phps1 (Millipore)

Name: shp2 inhibitor phps1
Brand: Millipore
Rating: 90 (1 reviews)

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Millipore shp2 inhibitor phps1

<t>SHP2</t> deficiency in macrophages protects mice from HFD-induced obesity by promoting energy expenditure. WT and cSHP2-KO mice were fed on NCD or HFD. A to C, body weight change (A and B) and food intake (C) were recorded. **, p < 0.01 versus corresponding time point from WT-HFD. Energy expenditure of HFD-fed WT and cSHP2-KO mice were monitored using CLAMS for 24 h. D, the curve of oxygen consumption rate (VO2). E, the carbon dioxide production rate (VCO2). F, heat production. Data are expressed as mean ± S.E., n = 6–8. *, p < 0.05.

Shp2 Inhibitor Phps1, supplied by Millipore, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Average 90 stars, based on 1 article reviews

shp2 inhibitor phps1 - by Bioz Stars, 2026-02

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1) Product Images from "Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels"

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

Journal: The Journal of Biological Chemistry

doi: 10.1074/jbc.RA119.011840

SHP2 deficiency in macrophages protects mice from HFD-induced obesity by promoting energy expenditure. WT and cSHP2-KO mice were fed on NCD or HFD. A to C, body weight change (A and B) and food intake (C) were recorded. **, p < 0.01 versus corresponding time point from WT-HFD. Energy expenditure of HFD-fed WT and cSHP2-KO mice were monitored using CLAMS for 24 h. D, the curve of oxygen consumption rate (VO2). E, the carbon dioxide production rate (VCO2). F, heat production. Data are expressed as mean ± S.E., n = 6–8. *, p < 0.05.

Figure Legend Snippet: SHP2 deficiency in macrophages protects mice from HFD-induced obesity by promoting energy expenditure. WT and cSHP2-KO mice were fed on NCD or HFD. A to C, body weight change (A and B) and food intake (C) were recorded. **, p < 0.01 versus corresponding time point from WT-HFD. Energy expenditure of HFD-fed WT and cSHP2-KO mice were monitored using CLAMS for 24 h. D, the curve of oxygen consumption rate (VO2). E, the carbon dioxide production rate (VCO2). F, heat production. Data are expressed as mean ± S.E., n = 6–8. *, p < 0.05.

Techniques Used:

Ablation of SHP2 in macrophages protects mice from HFD-induced insulin resistance. WT and cSHP2-KO mice were fed on NCD or HFD. A and B, glucose tolerance test and insulin tolerance test were performed on mice with 14 weeks of HFD feeding. C, hepatic gluconeogenesis was determined by PTT assay. *, p < 0.05; **, p < 0.01 versus corresponding time point from WT. D, Pepck and G6Pase mRNA level in liver was determined by qPCR. E, fasting insulin level in the serum was determined by ELISA. F, insulin signaling in liver was determined by Western blot analysis after 6 h of fasting. Data are expressed as mean ± S.E., n = 6–8. *, p < 0.05; ns, not significant.

Figure Legend Snippet: Ablation of SHP2 in macrophages protects mice from HFD-induced insulin resistance. WT and cSHP2-KO mice were fed on NCD or HFD. A and B, glucose tolerance test and insulin tolerance test were performed on mice with 14 weeks of HFD feeding. C, hepatic gluconeogenesis was determined by PTT assay. *, p < 0.05; **, p < 0.01 versus corresponding time point from WT. D, Pepck and G6Pase mRNA level in liver was determined by qPCR. E, fasting insulin level in the serum was determined by ELISA. F, insulin signaling in liver was determined by Western blot analysis after 6 h of fasting. Data are expressed as mean ± S.E., n = 6–8. *, p < 0.05; ns, not significant.

Techniques Used: Enzyme-linked Immunosorbent Assay, Western Blot

SHP2 deficiency in macrophages protects mice from HFD-induced hepatic steatosis. A, macroscopic appearance (left) and weight (right) of liver from WT and cSHP2-KO mice fed on NCD or HFD. B and C, H&E stain (left) and clinical score (right) (B) and caveolin-1 staining (C) of liver from WT and cSHP2-KO mice fed on HFD. D, TG in serum and liver from mice were measured. E, the expression of p-AMPK and p-ACC in liver of HFD mice was determined by Western blotting. Data are expressed as mean ± S.E. in panels A, B, and D, n = 8–12. *, p < 0.05.

Figure Legend Snippet: SHP2 deficiency in macrophages protects mice from HFD-induced hepatic steatosis. A, macroscopic appearance (left) and weight (right) of liver from WT and cSHP2-KO mice fed on NCD or HFD. B and C, H&E stain (left) and clinical score (right) (B) and caveolin-1 staining (C) of liver from WT and cSHP2-KO mice fed on HFD. D, TG in serum and liver from mice were measured. E, the expression of p-AMPK and p-ACC in liver of HFD mice was determined by Western blotting. Data are expressed as mean ± S.E. in panels A, B, and D, n = 8–12. *, p < 0.05.

Techniques Used: Staining, Expressing, Western Blot

Loss of SHP2 in macrophages promotes elevated IL-18 secretion and caspase-1 activation both in vivo and in vitro. A and B, after feeding on NCD or HFD for 16 weeks, mice were sacrificed. The levels of IL-1β and IL-18 in the serum were determined by ELISA (A), and caspase-1 (CASP1) activation in peripheral macrophages from mice was determined by Western blotting (B). C–F, Peritoneal macrophages obtained from WT and cSHP2-KO mice were stimulated with 100 ng/ml LPS in the presence of ceramide (0.1 mm) or palmitic acid (PA, 200 μm). The level of IL-18 in the supernatant was determined by ELISA (C and E); CASP1 activation was determined by Western blotting (D and F). Data are expressed as mean ± S.E. in panels A–E, n = 6 in A and n = 3 in C, E. *, p < 0.05; **, p < 0.01.

Figure Legend Snippet: Loss of SHP2 in macrophages promotes elevated IL-18 secretion and caspase-1 activation both in vivo and in vitro. A and B, after feeding on NCD or HFD for 16 weeks, mice were sacrificed. The levels of IL-1β and IL-18 in the serum were determined by ELISA (A), and caspase-1 (CASP1) activation in peripheral macrophages from mice was determined by Western blotting (B). C–F, Peritoneal macrophages obtained from WT and cSHP2-KO mice were stimulated with 100 ng/ml LPS in the presence of ceramide (0.1 mm) or palmitic acid (PA, 200 μm). The level of IL-18 in the supernatant was determined by ELISA (C and E); CASP1 activation was determined by Western blotting (D and F). Data are expressed as mean ± S.E. in panels A–E, n = 6 in A and n = 3 in C, E. *, p < 0.05; **, p < 0.01.

Techniques Used: Activation Assay, In Vivo, In Vitro, Enzyme-linked Immunosorbent Assay, Western Blot

SHP2 deficiency-caused increase of insulin sensitivity is almost blocked by caspase-1 deletion. WT, cSHP2-KO, and SHP2/caspase-1 double knockout (DKO) mice were fed on HFD for 16 weeks. A, body weight change was recorded. B and C, GTT and ITT assays were carried out after mice were on HFD for 14 weeks. D, fasting insulin level in the serum of mice was determined by ELISA. E, insulin signaling in liver was determined by Western blotting after 6 h fasting. Data are expressed as mean ± S.E. in panels A–E, n = 6-8. *, p < 0.05; **, p < 0.01 versus WT; #, P < 0.05 versus cSHP2-KO in panels A–C. *, p < 0.05 versus values indicated in panels D and E. ns, not significant.

Figure Legend Snippet: SHP2 deficiency-caused increase of insulin sensitivity is almost blocked by caspase-1 deletion. WT, cSHP2-KO, and SHP2/caspase-1 double knockout (DKO) mice were fed on HFD for 16 weeks. A, body weight change was recorded. B and C, GTT and ITT assays were carried out after mice were on HFD for 14 weeks. D, fasting insulin level in the serum of mice was determined by ELISA. E, insulin signaling in liver was determined by Western blotting after 6 h fasting. Data are expressed as mean ± S.E. in panels A–E, n = 6-8. *, p < 0.05; **, p < 0.01 versus WT; #, P < 0.05 versus cSHP2-KO in panels A–C. *, p < 0.05 versus values indicated in panels D and E. ns, not significant.

Techniques Used: Double Knockout, Enzyme-linked Immunosorbent Assay, Western Blot

The SHP2 inhibitor SHP099 improved hepatic steatosis and insulin resistance in HFD mice. C57BL/6 mice were fed on HFD for 16 weeks. After that, mice were i.p. treated with 2.5 and 5 mg/kg SHP099 for 16 days. A, change of body weight was recorded. B and C, GTT and ITT assays were performed. D and E, fasting level of insulin and IL-18 in serum was examined by ELISA. F and G, weight (F) and H&E staining (G) of liver from SHP099-treated and control mice. Scale bar, 50 μm. H, the expression of p-AMPK and p-ACC in liver of SHP099-treated and control mice was determined by Western blotting. I, insulin signaling in liver was determined by Western blotting after 6 h of fasting. Data are expressed as mean ± S.E., n = 6. *, p < 0.05; **, p < 0.01 versus HFD or as indicated.

Figure Legend Snippet: The SHP2 inhibitor SHP099 improved hepatic steatosis and insulin resistance in HFD mice. C57BL/6 mice were fed on HFD for 16 weeks. After that, mice were i.p. treated with 2.5 and 5 mg/kg SHP099 for 16 days. A, change of body weight was recorded. B and C, GTT and ITT assays were performed. D and E, fasting level of insulin and IL-18 in serum was examined by ELISA. F and G, weight (F) and H&E staining (G) of liver from SHP099-treated and control mice. Scale bar, 50 μm. H, the expression of p-AMPK and p-ACC in liver of SHP099-treated and control mice was determined by Western blotting. I, insulin signaling in liver was determined by Western blotting after 6 h of fasting. Data are expressed as mean ± S.E., n = 6. *, p < 0.05; **, p < 0.01 versus HFD or as indicated.

Techniques Used: Enzyme-linked Immunosorbent Assay, Staining, Expressing, Western Blot

The SHP2 inhibitor Phps1 ameliorated hepatic steatosis and insulin resistance in HFD mice. C57BL/6 mice were fed on HFD for 16 weeks. After that, mice were i.p. treated with 2 mg/kg Phps1 for 16 days. A, change of body weight was recorded. B and C, GTT and ITT assays were performed. D and E, fasting level of insulin and IL-18 in serum was examined by ELISA. F and G, macroscopic appearance (left) and weight (right) (F) and H&E staining (left) and clinical score (right) (G) of liver from Phps1-treated and control mice. Scale bar, 50 μm. H, caveolin-1 expression in liver was determined by immunofluorescence stain. I, the expression of p-AMPK and p-ACC in liver of Phps1-treated and control mice were determined by Western blotting. Data are expressed as mean ± S.E., n = 6. *, p < 0.05 versus HFD or as indicated.

Figure Legend Snippet: The SHP2 inhibitor Phps1 ameliorated hepatic steatosis and insulin resistance in HFD mice. C57BL/6 mice were fed on HFD for 16 weeks. After that, mice were i.p. treated with 2 mg/kg Phps1 for 16 days. A, change of body weight was recorded. B and C, GTT and ITT assays were performed. D and E, fasting level of insulin and IL-18 in serum was examined by ELISA. F and G, macroscopic appearance (left) and weight (right) (F) and H&E staining (left) and clinical score (right) (G) of liver from Phps1-treated and control mice. Scale bar, 50 μm. H, caveolin-1 expression in liver was determined by immunofluorescence stain. I, the expression of p-AMPK and p-ACC in liver of Phps1-treated and control mice were determined by Western blotting. Data are expressed as mean ± S.E., n = 6. *, p < 0.05 versus HFD or as indicated.

Techniques Used: Enzyme-linked Immunosorbent Assay, Staining, Expressing, Immunofluorescence, Western Blot

The graphic illustration for the mechanism of SHP2 regulating HFD-induced obesity and insulin resistance. Knockout of SHP2 in macrophage significantly ameliorates HFD-induced obesity and insulin resistance in mice through promoting caspase-1-dependent overproduction of IL-18. IL-18 promotes lipolysis in target tissues and alleviates the whole-body lipid accumulation as well as insulin resistance. More importantly, SHP2-specific inhibitor SHP099 and Phps1 significantly ameliorates HFD-induced insulin resistance and fat liver, indicating a potential drug target for treatment of insulin resistance.

Figure Legend Snippet: The graphic illustration for the mechanism of SHP2 regulating HFD-induced obesity and insulin resistance. Knockout of SHP2 in macrophage significantly ameliorates HFD-induced obesity and insulin resistance in mice through promoting caspase-1-dependent overproduction of IL-18. IL-18 promotes lipolysis in target tissues and alleviates the whole-body lipid accumulation as well as insulin resistance. More importantly, SHP2-specific inhibitor SHP099 and Phps1 significantly ameliorates HFD-induced insulin resistance and fat liver, indicating a potential drug target for treatment of insulin resistance.

Techniques Used: Knock-Out

Image Search Results

Bioinformatics analysis reveals the crucial role of the CBX2-NF-κB-METTL3-SHP2 pathway in oral squamous cell carcinoma. ( A ) Boxplot of sample correction; ( B ) PCA plot of differential samples; ( C ) Volcano plot of differential genes; ( D ) Ordered plot of differential genes; ( E ) Bar chart of GO enrichment analysis; ( F ) Bubble plot of KEGG enrichment analysis; ( G ) Lollipop chart of KEGG enrichment analysis; ( H ) Scatter plot of CBX2 and CEP55 correlation; ( I ) Scatter plot of CEP55 and NF-κB correlation; ( J ) Scatter plot of NF-κB and METTL3 correlation; ( K ) Scatter plot of METTL3 and SHP2 (PTPN11) correlation; ( L ) CBX2 expression levels and patient survival analysis.

Journal: Scientific Reports

Article Title: CBX2 promoted oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling induced metastasis/proliferation and angiogenesis

doi: 10.1038/s41598-025-31475-3

Figure Lengend Snippet: Bioinformatics analysis reveals the crucial role of the CBX2-NF-κB-METTL3-SHP2 pathway in oral squamous cell carcinoma. ( A ) Boxplot of sample correction; ( B ) PCA plot of differential samples; ( C ) Volcano plot of differential genes; ( D ) Ordered plot of differential genes; ( E ) Bar chart of GO enrichment analysis; ( F ) Bubble plot of KEGG enrichment analysis; ( G ) Lollipop chart of KEGG enrichment analysis; ( H ) Scatter plot of CBX2 and CEP55 correlation; ( I ) Scatter plot of CEP55 and NF-κB correlation; ( J ) Scatter plot of NF-κB and METTL3 correlation; ( K ) Scatter plot of METTL3 and SHP2 (PTPN11) correlation; ( L ) CBX2 expression levels and patient survival analysis.

Article Snippet: NF-κB activator E1351 and SHP2 inhibitor PHPS1 were purchased from MedChemExpress, USA.

Techniques: Expressing

Western blot and Co-IP results indicate that knockdown of CBX2, activation of NF-κB, inhibition of METTL3, overexpression of METTL3, and Inhibition of SHP2 all upregulate or downregulate downstream signaling molecules. ( A ) Western Blot analysis of protein bands for CBX2, CEP55, p-NF-κB, METTL3, TGFβ1, and p-SHP2 in the NC group, CBX2-KD group, CBX2-KD-E1351 group, CBX2-KD-E1351-STM2457 group, CBX2-KD-E1351-STM2457-METTL3-OE group, and CBX2-KD-E1351-STM2457-METTL3-OE-PHPS1 group, as well as statistical analysis graphs of relative protein expression levels. GAPDH was as a control protein; ( B ) Western Blot analysis of protein bands for p-PI3K, Slug, and Snail, along with statistical analysis graphs of relative protein expression levels. GAPDH was as the control protein; ( C ) Statistical analysis chart of the Co-IP experiment analyzing the interaction between endogenous CBX2 and CEP55 in SCC-25 cells. N = 6; Data are expressed as mean ± standard deviation; * P < 0.05; ** P < 0.01; ns P > 0.05.

Journal: Scientific Reports

Article Title: CBX2 promoted oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling induced metastasis/proliferation and angiogenesis

doi: 10.1038/s41598-025-31475-3

Figure Lengend Snippet: Western blot and Co-IP results indicate that knockdown of CBX2, activation of NF-κB, inhibition of METTL3, overexpression of METTL3, and Inhibition of SHP2 all upregulate or downregulate downstream signaling molecules. ( A ) Western Blot analysis of protein bands for CBX2, CEP55, p-NF-κB, METTL3, TGFβ1, and p-SHP2 in the NC group, CBX2-KD group, CBX2-KD-E1351 group, CBX2-KD-E1351-STM2457 group, CBX2-KD-E1351-STM2457-METTL3-OE group, and CBX2-KD-E1351-STM2457-METTL3-OE-PHPS1 group, as well as statistical analysis graphs of relative protein expression levels. GAPDH was as a control protein; ( B ) Western Blot analysis of protein bands for p-PI3K, Slug, and Snail, along with statistical analysis graphs of relative protein expression levels. GAPDH was as the control protein; ( C ) Statistical analysis chart of the Co-IP experiment analyzing the interaction between endogenous CBX2 and CEP55 in SCC-25 cells. N = 6; Data are expressed as mean ± standard deviation; * P < 0.05; ** P < 0.01; ns P > 0.05.

Article Snippet: NF-κB activator E1351 and SHP2 inhibitor PHPS1 were purchased from MedChemExpress, USA.

Techniques: Western Blot, Co-Immunoprecipitation Assay, Knockdown, Activation Assay, Inhibition, Over Expression, Expressing, Control, Standard Deviation

Scratch, Transwell, and Colony Formation Experiments Indicate That Knockdown of CBX2, Activation of NF-κB, Inhibition of METTL3, Overexpression of METTL3, and Inhibition of SHP2 All Inhibit or Promote Tumor Cell Migration, Invasion, and Proliferation. ( A ) Analysis of scratch test results for NC group, CBX2-KD group, CBX2-KD-E1351 group, CBX2-KD-E1351-STM2457 group, CBX2-KD-E1351-STM2457-METTL3-OE group, and CBX2-KD-E1351-STM2457-METTL3-OE-PHPS1 group at 0 hours and 48 hours, as well as statistical analysis of scratch distance; ( B ) Analysis of Transwell experiment for SCC-25 cells, including the experimental results images for cell migration and invasion, as well as statistical analysis charts of the number of migrating and invading cells; ( C ) Colony formation analysis of the experimental results graph showing the proliferation of SCC-25 cells in experiments, as well as the statistical analysis graph of the number of clone cells. N=6; Data are expressed as mean ± standard deviation; * P < 0.05; ** P < 0.01; ns P > 0.05.

Journal: Scientific Reports

Article Title: CBX2 promoted oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling induced metastasis/proliferation and angiogenesis

doi: 10.1038/s41598-025-31475-3

Figure Lengend Snippet: Scratch, Transwell, and Colony Formation Experiments Indicate That Knockdown of CBX2, Activation of NF-κB, Inhibition of METTL3, Overexpression of METTL3, and Inhibition of SHP2 All Inhibit or Promote Tumor Cell Migration, Invasion, and Proliferation. ( A ) Analysis of scratch test results for NC group, CBX2-KD group, CBX2-KD-E1351 group, CBX2-KD-E1351-STM2457 group, CBX2-KD-E1351-STM2457-METTL3-OE group, and CBX2-KD-E1351-STM2457-METTL3-OE-PHPS1 group at 0 hours and 48 hours, as well as statistical analysis of scratch distance; ( B ) Analysis of Transwell experiment for SCC-25 cells, including the experimental results images for cell migration and invasion, as well as statistical analysis charts of the number of migrating and invading cells; ( C ) Colony formation analysis of the experimental results graph showing the proliferation of SCC-25 cells in experiments, as well as the statistical analysis graph of the number of clone cells. N=6; Data are expressed as mean ± standard deviation; * P < 0.05; ** P < 0.01; ns P > 0.05.

Article Snippet: NF-κB activator E1351 and SHP2 inhibitor PHPS1 were purchased from MedChemExpress, USA.

Techniques: Knockdown, Activation Assay, Inhibition, Over Expression, Migration, Standard Deviation

Western blot and tubulogenesis experiment results show that knockdown of CBX2, activation of NF-κB, inhibition of METTL3, overexpression of METTL3, and inhibition of SHP2 all inhibit or promote angiogenesis. ( A ) Western Blot analysis of VEGFA and HIF1α protein bands in the NC group, CBX2-KD group, CBX2-KD-E1351 group, CBX2-KD-E1351-STM2457 group, CBX2-KD-E1351-STM2457-METTL3-OE group, and CBX2-KD-E1351-STM2457-METTL3-OE-PHPS1 group, along with statistical analysis graphs of relative protein expression levels. GAPDH are as the control protein; ( B ) Tubulogenesis analysis of experimental results, including figures showing the formation of tube-like structures and statistical analysis of the number of neovessels per visual field. N=6; Data are expressed as mean ± standard deviation; * P < 0.05; ** P < 0.01; ns P > 0.05.

Journal: Scientific Reports

Article Title: CBX2 promoted oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling induced metastasis/proliferation and angiogenesis

doi: 10.1038/s41598-025-31475-3

Figure Lengend Snippet: Western blot and tubulogenesis experiment results show that knockdown of CBX2, activation of NF-κB, inhibition of METTL3, overexpression of METTL3, and inhibition of SHP2 all inhibit or promote angiogenesis. ( A ) Western Blot analysis of VEGFA and HIF1α protein bands in the NC group, CBX2-KD group, CBX2-KD-E1351 group, CBX2-KD-E1351-STM2457 group, CBX2-KD-E1351-STM2457-METTL3-OE group, and CBX2-KD-E1351-STM2457-METTL3-OE-PHPS1 group, along with statistical analysis graphs of relative protein expression levels. GAPDH are as the control protein; ( B ) Tubulogenesis analysis of experimental results, including figures showing the formation of tube-like structures and statistical analysis of the number of neovessels per visual field. N=6; Data are expressed as mean ± standard deviation; * P < 0.05; ** P < 0.01; ns P > 0.05.

Article Snippet: NF-κB activator E1351 and SHP2 inhibitor PHPS1 were purchased from MedChemExpress, USA.

Techniques: Western Blot, Knockdown, Activation Assay, Inhibition, Over Expression, Expressing, Control, Standard Deviation

Schematic illustration of CBX2 promoting oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling, inducing metastasis/proliferation, and angiogenesis.

Journal: Scientific Reports

Article Title: CBX2 promoted oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling induced metastasis/proliferation and angiogenesis

doi: 10.1038/s41598-025-31475-3

Figure Lengend Snippet: Schematic illustration of CBX2 promoting oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling, inducing metastasis/proliferation, and angiogenesis.

Article Snippet: NF-κB activator E1351 and SHP2 inhibitor PHPS1 were purchased from MedChemExpress, USA.

Techniques:

Bioinformatics Analysis of AML. ( A ) Volcano plots of differential genes in the GSE10358 and GSE24395 datasets; ( B ) Venn diagram of differential genes; ( C ) Bar chart of GO enrichment analysis; ( D ) Bubble chart of KEGG enrichment analysis; ( E ) Scatter plot of the correlation between Src and SHP2 (PTPN11); ( F ) Scatter plot of the correlation between SHP2 (PTPN11) and ERK1/2 (MAPK1); ( G ) Scatter plot of the correlation between IL-3 and Siglec6.

Journal: Scientific Reports

Article Title: Siglec6 CAR T cells suppressed progression of AML via inhibiting Siglec6 and SHP2 induced Src and ERK signaling activation

doi: 10.1038/s41598-025-00456-x

Figure Lengend Snippet: Bioinformatics Analysis of AML. ( A ) Volcano plots of differential genes in the GSE10358 and GSE24395 datasets; ( B ) Venn diagram of differential genes; ( C ) Bar chart of GO enrichment analysis; ( D ) Bubble chart of KEGG enrichment analysis; ( E ) Scatter plot of the correlation between Src and SHP2 (PTPN11); ( F ) Scatter plot of the correlation between SHP2 (PTPN11) and ERK1/2 (MAPK1); ( G ) Scatter plot of the correlation between IL-3 and Siglec6.

Article Snippet: A portion of MOLM-13 cells were treated with 10 μg/mL of SHP2 inhibitor (PHPS1, MCE), 10 μg/mL of Src inhibitor (S1021, Selleck), and 5 μg/mL SHP2 agonist (75330-75-5, Merck) for 12 h to promote and inhibit protein expression levels.

Techniques:

Siglec6 Acts on AML through the SHP2/Src/ERK/IL-3 Axis. ( A ) Western blot detects the protein expression levels of Siglec6, p-SHP2, IL-3, pERK1/2 in AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; GAPDH as control protein; ( B ) Immunofluorescence detects the protein expression levels of Siglec6 and p-SHP2 in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups. Data are expressed as mean ± standard deviation. N = 3; * P < 0.05; ** P < 0.01; ns P >0.05.

Journal: Scientific Reports

Article Title: Siglec6 CAR T cells suppressed progression of AML via inhibiting Siglec6 and SHP2 induced Src and ERK signaling activation

doi: 10.1038/s41598-025-00456-x

Figure Lengend Snippet: Siglec6 Acts on AML through the SHP2/Src/ERK/IL-3 Axis. ( A ) Western blot detects the protein expression levels of Siglec6, p-SHP2, IL-3, pERK1/2 in AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; GAPDH as control protein; ( B ) Immunofluorescence detects the protein expression levels of Siglec6 and p-SHP2 in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups. Data are expressed as mean ± standard deviation. N = 3; * P < 0.05; ** P < 0.01; ns P >0.05.

Techniques: Western Blot, Expressing, Control, Immunofluorescence, Standard Deviation

Siglec6 Promotes the Proliferation and Invasion-Metastasis Abilities of AML through the SHP2/Src/ERK/IL-3 Axis. ( A ) Western blot detects the expression levels of MMP2, MMP9, CyclinA1, CyclinD1 proteins in AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; ( B ) Transwell assay detects the invasion ability of AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; ( C ) CCK8 assay detects the proliferation ability of AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; ( D ) Western blot detects the expression levels of Ki-67 in AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; GAPDH as control protein; Data are expressed as mean ± standard deviation. N = 3; * P < 0.05; ** P < 0.01; ns P >0.05.

Journal: Scientific Reports

Article Title: Siglec6 CAR T cells suppressed progression of AML via inhibiting Siglec6 and SHP2 induced Src and ERK signaling activation

doi: 10.1038/s41598-025-00456-x

Figure Lengend Snippet: Siglec6 Promotes the Proliferation and Invasion-Metastasis Abilities of AML through the SHP2/Src/ERK/IL-3 Axis. ( A ) Western blot detects the expression levels of MMP2, MMP9, CyclinA1, CyclinD1 proteins in AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; ( B ) Transwell assay detects the invasion ability of AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; ( C ) CCK8 assay detects the proliferation ability of AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; ( D ) Western blot detects the expression levels of Ki-67 in AML cells in the oe-NC, oe-Siglec6, oe-Siglec6 + PHPS1, oe-Siglec6 + Dasatinib, oe-Siglec6 + Dasatinib + Lovastatin, and oe-Siglec6 + Dasatinib + Lovastatin + IL-3 monoclonal antibody groups; GAPDH as control protein; Data are expressed as mean ± standard deviation. N = 3; * P < 0.05; ** P < 0.01; ns P >0.05.

Techniques: Western Blot, Expressing, Transwell Assay, CCK-8 Assay, Control, Standard Deviation

Siglec6 CAR T cells suppressed progression of AML via inhibiting Siglec6/ SHP2/ Src/ IL-3/ ERK signaling.

Journal: Scientific Reports

Article Title: Siglec6 CAR T cells suppressed progression of AML via inhibiting Siglec6 and SHP2 induced Src and ERK signaling activation

doi: 10.1038/s41598-025-00456-x

Figure Lengend Snippet: Siglec6 CAR T cells suppressed progression of AML via inhibiting Siglec6/ SHP2/ Src/ IL-3/ ERK signaling.

Techniques:

Journal: The Journal of Biological Chemistry

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

doi: 10.1074/jbc.RA119.011840

Figure Lengend Snippet: SHP2 deficiency in macrophages protects mice from HFD-induced obesity by promoting energy expenditure. WT and cSHP2-KO mice were fed on NCD or HFD. A to C, body weight change (A and B) and food intake (C) were recorded. **, p < 0.01 versus corresponding time point from WT-HFD. Energy expenditure of HFD-fed WT and cSHP2-KO mice were monitored using CLAMS for 24 h. D, the curve of oxygen consumption rate (VO2). E, the carbon dioxide production rate (VCO2). F, heat production. Data are expressed as mean ± S.E., n = 6–8. *, p < 0.05.

Article Snippet: The SHP2 inhibitor PHPS1 was purchased from Calbiochem (La Jolla, CA).

Techniques:

Journal: The Journal of Biological Chemistry

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

doi: 10.1074/jbc.RA119.011840

Figure Lengend Snippet: Ablation of SHP2 in macrophages protects mice from HFD-induced insulin resistance. WT and cSHP2-KO mice were fed on NCD or HFD. A and B, glucose tolerance test and insulin tolerance test were performed on mice with 14 weeks of HFD feeding. C, hepatic gluconeogenesis was determined by PTT assay. *, p < 0.05; **, p < 0.01 versus corresponding time point from WT. D, Pepck and G6Pase mRNA level in liver was determined by qPCR. E, fasting insulin level in the serum was determined by ELISA. F, insulin signaling in liver was determined by Western blot analysis after 6 h of fasting. Data are expressed as mean ± S.E., n = 6–8. *, p < 0.05; ns, not significant.

Article Snippet: The SHP2 inhibitor PHPS1 was purchased from Calbiochem (La Jolla, CA).

Techniques: Enzyme-linked Immunosorbent Assay, Western Blot

Journal: The Journal of Biological Chemistry

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

doi: 10.1074/jbc.RA119.011840

Figure Lengend Snippet: SHP2 deficiency in macrophages protects mice from HFD-induced hepatic steatosis. A, macroscopic appearance (left) and weight (right) of liver from WT and cSHP2-KO mice fed on NCD or HFD. B and C, H&E stain (left) and clinical score (right) (B) and caveolin-1 staining (C) of liver from WT and cSHP2-KO mice fed on HFD. D, TG in serum and liver from mice were measured. E, the expression of p-AMPK and p-ACC in liver of HFD mice was determined by Western blotting. Data are expressed as mean ± S.E. in panels A, B, and D, n = 8–12. *, p < 0.05.

Article Snippet: The SHP2 inhibitor PHPS1 was purchased from Calbiochem (La Jolla, CA).

Techniques: Staining, Expressing, Western Blot

Journal: The Journal of Biological Chemistry

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

doi: 10.1074/jbc.RA119.011840

Figure Lengend Snippet: Loss of SHP2 in macrophages promotes elevated IL-18 secretion and caspase-1 activation both in vivo and in vitro. A and B, after feeding on NCD or HFD for 16 weeks, mice were sacrificed. The levels of IL-1β and IL-18 in the serum were determined by ELISA (A), and caspase-1 (CASP1) activation in peripheral macrophages from mice was determined by Western blotting (B). C–F, Peritoneal macrophages obtained from WT and cSHP2-KO mice were stimulated with 100 ng/ml LPS in the presence of ceramide (0.1 mm) or palmitic acid (PA, 200 μm). The level of IL-18 in the supernatant was determined by ELISA (C and E); CASP1 activation was determined by Western blotting (D and F). Data are expressed as mean ± S.E. in panels A–E, n = 6 in A and n = 3 in C, E. *, p < 0.05; **, p < 0.01.

Article Snippet: The SHP2 inhibitor PHPS1 was purchased from Calbiochem (La Jolla, CA).

Techniques: Activation Assay, In Vivo, In Vitro, Enzyme-linked Immunosorbent Assay, Western Blot

Journal: The Journal of Biological Chemistry

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

doi: 10.1074/jbc.RA119.011840

Figure Lengend Snippet: SHP2 deficiency-caused increase of insulin sensitivity is almost blocked by caspase-1 deletion. WT, cSHP2-KO, and SHP2/caspase-1 double knockout (DKO) mice were fed on HFD for 16 weeks. A, body weight change was recorded. B and C, GTT and ITT assays were carried out after mice were on HFD for 14 weeks. D, fasting insulin level in the serum of mice was determined by ELISA. E, insulin signaling in liver was determined by Western blotting after 6 h fasting. Data are expressed as mean ± S.E. in panels A–E, n = 6-8. *, p < 0.05; **, p < 0.01 versus WT; #, P < 0.05 versus cSHP2-KO in panels A–C. *, p < 0.05 versus values indicated in panels D and E. ns, not significant.

Article Snippet: The SHP2 inhibitor PHPS1 was purchased from Calbiochem (La Jolla, CA).

Techniques: Double Knockout, Enzyme-linked Immunosorbent Assay, Western Blot

Journal: The Journal of Biological Chemistry

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

doi: 10.1074/jbc.RA119.011840

Figure Lengend Snippet: The SHP2 inhibitor SHP099 improved hepatic steatosis and insulin resistance in HFD mice. C57BL/6 mice were fed on HFD for 16 weeks. After that, mice were i.p. treated with 2.5 and 5 mg/kg SHP099 for 16 days. A, change of body weight was recorded. B and C, GTT and ITT assays were performed. D and E, fasting level of insulin and IL-18 in serum was examined by ELISA. F and G, weight (F) and H&E staining (G) of liver from SHP099-treated and control mice. Scale bar, 50 μm. H, the expression of p-AMPK and p-ACC in liver of SHP099-treated and control mice was determined by Western blotting. I, insulin signaling in liver was determined by Western blotting after 6 h of fasting. Data are expressed as mean ± S.E., n = 6. *, p < 0.05; **, p < 0.01 versus HFD or as indicated.

Article Snippet: The SHP2 inhibitor PHPS1 was purchased from Calbiochem (La Jolla, CA).

Techniques: Enzyme-linked Immunosorbent Assay, Staining, Expressing, Western Blot

Journal: The Journal of Biological Chemistry

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

doi: 10.1074/jbc.RA119.011840

Figure Lengend Snippet: The SHP2 inhibitor Phps1 ameliorated hepatic steatosis and insulin resistance in HFD mice. C57BL/6 mice were fed on HFD for 16 weeks. After that, mice were i.p. treated with 2 mg/kg Phps1 for 16 days. A, change of body weight was recorded. B and C, GTT and ITT assays were performed. D and E, fasting level of insulin and IL-18 in serum was examined by ELISA. F and G, macroscopic appearance (left) and weight (right) (F) and H&E staining (left) and clinical score (right) (G) of liver from Phps1-treated and control mice. Scale bar, 50 μm. H, caveolin-1 expression in liver was determined by immunofluorescence stain. I, the expression of p-AMPK and p-ACC in liver of Phps1-treated and control mice were determined by Western blotting. Data are expressed as mean ± S.E., n = 6. *, p < 0.05 versus HFD or as indicated.

Article Snippet: The SHP2 inhibitor PHPS1 was purchased from Calbiochem (La Jolla, CA).

Techniques: Enzyme-linked Immunosorbent Assay, Staining, Expressing, Immunofluorescence, Western Blot

Journal: The Journal of Biological Chemistry

Article Title: Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

doi: 10.1074/jbc.RA119.011840

Figure Lengend Snippet: The graphic illustration for the mechanism of SHP2 regulating HFD-induced obesity and insulin resistance. Knockout of SHP2 in macrophage significantly ameliorates HFD-induced obesity and insulin resistance in mice through promoting caspase-1-dependent overproduction of IL-18. IL-18 promotes lipolysis in target tissues and alleviates the whole-body lipid accumulation as well as insulin resistance. More importantly, SHP2-specific inhibitor SHP099 and Phps1 significantly ameliorates HFD-induced insulin resistance and fat liver, indicating a potential drug target for treatment of insulin resistance.

Article Snippet: The SHP2 inhibitor PHPS1 was purchased from Calbiochem (La Jolla, CA).

Techniques: Knock-Out

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