Research Resource: Identification of Novel Growth Hormone-Regulated Phosphorylation Sites by Quantitative Phosphoproteomics

Ray, Bridgette N.; Kweon, Hye Kyong; Argetsinger, Lawrence S.; Fingar, Diane C.; Andrews, Philip C.; Carter-Su, Christin

GH elicits a diverse range of cellular responses, including secretion of IGF-I and promotion of cell proliferation and differentiation. GH signaling is initiated by GH binding to a GH receptor dimer, which leads to activation of the GH receptor-associated Janus kinase 2 (JAK2) (5, 6) . The activated JAK2 phosphorylates tyrosines within itself and the GH receptor, forming binding sites for Src Homology (SH2) and phosphotyrosine binding domain-containing proteins, such as the signal transducers and activators of transcription (Stats) (reviewed in Refs. 7 and 8) . In addition to signaling through Stats, GH activates the Ras/Raf/MAPK kinase (MEK)1/Erks 1/2 pathway (9, 10) and the phosphatidylinositol 3-kinase (PI3K)/Akt/mTORC1 pathway (11) (12) (13) (14) . GH has also been shown, often in a cell-specific manner, to activate members of the Src family of tyrosine kinases (15) and to stimulate the tyrosyl phosphorylation of a variety of other proteins, including transmembrane proteins (e.g. SIRP1␣), phosphatases (e.g. SHP2), adapter proteins (e.g. SH2B1, CrkII), and proteins associated with the cytoskeleton (e.g. p130Cas/Bcar1) (16 -18) . Although investigation of these GH-regulated proteins has given us insight into some of the ways in which cells respond to GH, we hypothesized that these proteins most likely represent only a small subset of the proteins that undergo GH-dependent phosphorylation and thus contribute to cells' diverse responses to GH.