Table 1.

Binding Partners of SHP-2 in Gastrointestinal Cells

Organs	Proteins	Interactions	Cell types	Cell outcomes	References
Stomach	CagA	SH2 domain of SHP-2 and phosphorylated tyrosine in the EPIYA motif of CagA	AGS cells Human gastric epithelial cells	Increased phosphatase activity of SHP-2 ↓ Induction of the hummingbird phenotype	47, 59, 62, 117, 118
FAK	SHP-2 in complex with CagA and FAK	AGS cells	Dephosphorylation of FAK on Y397, Y576, and Y577 by SHP-2 ↓ Induction of the hummingbird phenotype	119
gp130	SHP-2 in complex with gp130	AGS cells	Activation of ERK1/2 by gp130 Inhibition of the Jak2/STAT3 pathway by SHP-2	59
Parafibromin	SH2 domain of SHP-2 and parafibromin	AGS cells	Dephosphorylation of parafibromin on Y290, Y293, and Y315 by SHP-2 ↓ Interaction between dephosphorylated parafibromin and β-catenin ↓ Nuclear accumulation of β-catenin and transcription of Wnt/β-catenin target genes	30
YAP and TAZ	C-terminal tail of SHP-2 and WW domain and C-terminus PDZ-binding motif of TAZ	AGS cells	Dephosphorylation of YAP/TAZ by SHP-2 ↓ Nuclear accumulation of SHP-2 ↓ Interaction between dephosphorylated parafibromin ↓ Transcription of TEAD-regulated genes	31
Intestine	IL22R1	SHP-2 and phosphorylated IL22R1 (Y251, Y301)	SW480 cells	Activation of the ERK1/2 and Jak/STAT3 signaling pathways by IL22	120
Bgp1	N-SH2 domain of SHP-2 and phosphorylated Y in the ITIM motif of Bgp1	CT51 cells	ND	121
Liver	FRS2α	SH2 domain of SHP-2 and phosphorylated Y of FRS2α	Hep3B cells Mouse hepatic cells	Activation of the ERK1/2 pathway by FGFR4	105
Gab1	SH2 domain of SHP-2 and phosphorylated Y of Gab1	Hep3B cells Hep2G cells Mouse hepatic cells	Activation of the ERK1/2 pathway	90, 105, 122
Liver and pancreas	COP1 FASN	N-SH2 domain of SHP-2 in a complex, association with FASN and COP1	Mouse hepatic cells Mouse pancreatic cells	FASN ubiquitination and degradation ↓ Impact on lipid metabolism and glucose homeostasis	101
Pancreas	p85/PI3K IRS2	SHP-2 in a complex with p85 and IRS2	INS-1 832/13 pancreatic cells	Glucose-induced activation of the Akt/FoxO1 pathway ↓ Insulin production	98
Sprouty 1	ND	INS-1 832/13 cells	Dephosphorylation of Sprouty 1 on Y by SHP-2 ↓ Glucose-induced activation of the ERK1/2 pathway ↓ Insulin production	98

AGS, human gastric carcinoma cells; Bgp1, biliary glycoprotein 1; COP1, constitutive photomorphogenesis protein 1; CT51, mouse colonic carcinoma cells; EPIYA, Glu-Pro-Ile-Tyr-Ala; FAK, focal adhesion kinase; FASN, fatty acid synthase; FRS2α, fibroblast growth factor receptor substrate 2 α; Gab1, Grb2-associated binding protein; Hep, human hepatocellular carcinoma cells; IL22R1, interleukin-22 receptor 1; INS-1 832/13 cells, insulin-producing β-cells; IRS2, insulin receptor substrate 2; ITIM, immunoreceptor tyrosine-based inhibitor motif; ND, not determined; SW480, human colonic adenocarcinoma cells; TAZ, transcriptional coactivator with PDZ-binding motif; Y, tyrosine; gp130, glycoprotein 130; YAP, yes-associated protein.