Ignet

Gene Information

Gene symbol: GRAP2

Gene name: GRB2-related adaptor protein 2

HGNC ID: 4563

Synonyms: Grf40, GrbX, GRBLG, GADS, Mona

Related Genes

#	Gene Symbol	Number of hits
1	ADIPOQ	1 hits
2	EGR1	1 hits
3	FOS	1 hits
4	GAB1	1 hits
5	GRB10	1 hits
6	GRB2	1 hits
7	IGF1	1 hits
8	IGF1R	1 hits
9	INS	1 hits
10	INSR	1 hits
11	IRS1	1 hits
12	IRS4	1 hits
13	MAPK1	1 hits
14	MAPK3	1 hits
15	MAPK6	1 hits
16	PIK3CA	1 hits
17	PIK3R1	1 hits
18	RAC2	1 hits
19	SHC1	1 hits
20	XPNPEP3	1 hits

Related Sentences

#	PMID	Sentence
1	9006901	Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains.
2	9006901	cDNA clones encoding human (h) Grb7 and a previously unknown protein with high homology to hGrb-IR and mGrb10 (where m indicates mouse) were found by screening expressed sequence tag data bases. hGrb7 mRNA expression is greatest in pancreas and restricted to a few other tissues.
3	9006901	In cells, Grb-IRbeta/Grb10 protein translocates from cytosol to membrane upon insulin stimulation, most likely due to direct interactions with the insulin receptor.
4	9006901	Studies with mutated receptors and synthetic phosphopeptides show that the hGrb-IRbeta/Grb10 SH2 domain binds at least two sites in the insulin receptor: the kinase activation loop > the juxtamembrane site. hGrb-IRbeta/Grb10 also binds a 135-kDa phosphoprotein in unstimulated 3T3-L1 adipocytes; binding is reduced upon insulin stimulation.
5	9006901	In addition, the c-Abl SH3 domain binds Grb-IR/Grb10, whereas Fyn, phosphatidylinositol 3-kinase p85, and Grb2 SH3 domains do not.
6	9006901	The site of c-Abl SH3 domain interaction is highly conserved within the Grb-IR/Grb10/Grb7/Grb14 family. hGrb-IRbeta/Grb10 also binds platelet-derived growth factor and epidermal growth factor receptors, suggesting a broader role in the signaling pathways of numerous receptors.
7	9006901	We conclude that hGrb-IRbeta/Grb10 is a widely expressed, PH and SH2 domain-containing, SH3 domain-binding protein that functions downstream from activated insulin and growth factor receptors.
8	9398740	This observation led to the hypothesis that these amino acid substitutions may impair the function of IRS-1, thereby causing the insulin resistance seen in patients with NIDDM.
9	9398740	We constructed four IRS-1 expression vectors for transfection in COS-7 cells: wild-type, single mutant (Gly819-->Arg), double mutant (Gly819-->Arg; Gly972-->Arg), and triple mutant (Gly819-->Arg; Gly972-->Arg; Arg1221-->Cys) IRS-1.
10	9398740	The mutations did not alter the level of expression or the extent of insulin receptor-mediated tyrosine phosphorylation of recombinant IRS-1.
11	9398740	Moreover, the mutations did not lead to a detectable impairment in the association of recombinant IRS-1 with important downstream effectors, including the p85 subunit of phosphatidylinositol 3-kinase and growth factor receptor-binding protein-2.
12	10744748	The insulin receptor substrate (IRS) family of proteins mediate a variety of intracellular signaling events by serving as signaling platforms downstream of several receptor tyrosine kinases including the insulin and insulin-like growth factor-1 (IGF-1) receptors.
13	10744748	Recently, several new members of this family have been identified including IRS-3, IRS-4, and growth factor receptor-binding protein 2-associated binder-1 (Gab-1). 3T3 cell lines derived from IRS-1-deficient embryos exhibit a 70-80% reduction in IGF-1-stimulated S-phase entry and a parallel decrease in the induction of the immediate-early genes c-fos and egr-1 but unaltered activation of the mitogen-activated protein kinases extracellular signal-regulated kinase-1 and extracellular signal-regulated kinase-2.
14	10744748	Overexpression of Gab-1 in IRS-1-deficient fibroblasts also results in the restoration of egr-1 induction to levels similar to those achieved by IRS-1 reconstitution and markedly increases IGF-1-stimulated S-phase progression.
15	10744748	Gab-1 is capable of regulating these biological end points despite the absence of IGF-1 stimulated tyrosine phosphorylation.
16	10744748	These data provide evidence that Gab-1 may serve as a unique signaling intermediate in insulin/IGF-1 signaling for induction of early gene expression and stimulation of mitogenesis without direct tyrosine phosphorylation.
17	11872675	Increased insulin sensitivity in IGF-I receptor--deficient brown adipocytes.
18	11872675	Immortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR(-/-)), as well as from fetuses of wild-type mice (IGF-IR(+/+)).
19	11872675	IGF-IR(-/-) brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells.
20	11872675	Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR(-/-) brown adipocytes, although IRS-1 protein content was reduced.
21	11872675	Downstream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR(-/-) brown adipocyte cell line.
22	11872675	However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR--deficient brown adipocytes.
23	11872675	These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation.
24	11872675	In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells.
25	11872675	Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation.
26	11872675	However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation.
27	11872675	Data presented here provide strong evidence that IGF-IR--deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin.
28	11954667	The protein content of insulin receptors and SRC homology adaptor protein (SHC) did not change significantly along the time frame analyzed.
29	11954667	However, insulin-induced tyrosine phosphorylation of the insulin receptor and SHC, and the association of SHC/growth factor receptor binding protein-2 (GRB2) decreased significantly from d 1 to wk 60 of life in both types of tissues.
30	11954667	Moreover, the expression of SH protein tyrosine phosphatase-2 (SHP2), a tyrosine phosphatase involved in insulin signal transduction and regulation of the insulin signal, decreased significantly with age progression, in both the forebrain cortex and the cerebellum of rats.
31	19654439	Seven nucleotide polymorphisms in three candidate genes, Rac2, Grap2, and Xpnpep3, located within a 3.3-Mb region were not found in 14 other inbred rat strains.
32	22923474	In this study, we show that pancreas-specific knockout of growth factor receptor-binding protein 10 (Grb10), which is highly expressed in pancreas and islets, leads to elevated insulin/IGF-1 signaling in islets, enhanced β-cell mass and insulin content, and increased insulin secretion in mice.