SHP-1 activation and modulation on ghrelin signaling to Akt

Model of SHP-1 activation and modulation on ghrelin signaling to Akt. Ghrelin binding to GHS-R1a activates the generation of the second messenger PtdIns(3,4,5)P3 (PIP3) by PI3K activation through Gi/o protein–dependent signaling pathway. Akt translocates to the plasma membrane by binding to PIP3, where it is phosphorylated at Y by the membrane-bound cSrc. Activation of cSrc induced phosphorylation of SHP-1, attenuation of p85 subunit from PI3K and PDK1, and phosphorylation of Akt. SHP-1 activation regulates cSrc activity by attenuation of Y416 phosphorylation. Once the receptor is activated, a second signaling pathway is mediated by β-arrestins 1 and 2, involving the recruitment of GHS-R1a, cSrc, SHP-1, and Akt into a β-arrestin–scaffolded complex.

Publication

The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system. (2011) Maria Lodeiro, et al. Mol Biol Cell. 2011 Nov 1;22(21):4182-4191. Figure: F5. All organisms Mus musculus Rattus norvegicus Bos taurus Capra hircus Oryctolagus cuniculus Homo sapiens Drosophila melanogaster

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