Growth hormone receptor binds Lyn Authored: Jupe, S, 2010-10-14 Edited: Jupe, S, 2011-06-10 Pubmed12218045 Pubmed12734187 Pubmed18488018 Reactome Database ID Release 431168456 Reactome, http://www.reactome.org ReactomeREACT_111139 Reviewed: Herington, AC, 2011-06-13 Reviewed: Waters, MJ, 2011-06-23 There is accumulating evidence that GH signalling utilises a Src family tyrosine kinase independently of JAK2, and that this is linked to activation of extracellular regulated kinases (ERKs) 1 and 2 (p44/42 MAPK). The relative strengths of these signaling pathways probably depends on cell type and may be mediated by conformational changes that are a consequence of ligand binding (Rowlinson et al. 2007). In NIH-3T3 cells GH activated c-Src, which in turn activated ERK1/2 via a pathway involving the activation of the Ras-like small GTPases RalA and RalB, leading to Elk-1 mediated transcription (Zhu et al. 2002). JAK2 and c-Src were both found to activate the Ras-like small GTPases Rap1 and Rap2 which inhibit RalA mediated activation of ERK1/2 (Ling et al. 2003). Src kinase inhibition was found to block ERK activation by GH. The major contributing kinase was identified as Lyn, which was found to co-immunoprecipitate with GHR and bind to the proximal 150 residues of the cytoplasmic domain (Rowlinson et al. 2007). Growth Hormone:Growth Hormone Receptor-JAK2 dimer:LYN Growth Hormone: Growth Hormone Receptor-JAK2 dimer