Intracellular pathway associated with GHR activation in hepatocytes. GH exerts its effect by binding to the extracellular domain of the GHR, where one molecule of GH binds two GHRs increasing the affinity of both receptors for two molecules of JAK2, which phosphorylate the GHR. GHR activation, in turn, triggers the activation of several signal transduction pathways, including STAT and PI3K through IRS. IRS and PI3K can activate nuclear transcription factors, including c-FOS and c-JUN, to induce cell proliferation and differentiation but also can increase glucose transport. GH-induced JAK2 activation phosphorilates STAT5 which translocates into the nucleus where binds to response elements in the regulatory regions of target genes including IGF1 and EGFR. The activation of adaptor protein SHC leads to the activation of MAPK involved in cell proliferation and growth.