Growth hormone receptor signaling

Growth hormone receptor signaling Growth hormone (Somatotropin or GH) is a key factor in determining lean body mass, stimulating the growth and metabolism of muscle, bone and cartilage cells, while reducing body fat. It has many other roles; it acts to regulate cell growth, differentiation, apoptosis, and reorganisation of the cytoskeleton, affecting diverse processes such as cardiac function, immune function, brain function, and aging. GH also has insulin-like effects such as stimulating amino acid transport, protein synthesis, glucose transport, and lipogenesis. The growth hormone receptor (GHR) is a a member of the cytokine receptor family. When the dimeric receptor binds GH it undergoes a conformational change which leads to phosphorylation of key tyrosine residues in its cytoplasmic domains and activation of associated tyrosine kinase JAK2. This leads to recruitment of signaling molecules such as STAT5 and Src family kinases such as Lyn leading to ERK activation. The signal is attenuated by association of Suppressor of Cytokine Signaling (SOCS) proteins and SHP phosphatases which bind to or dephosphorylate specific phosphorylated tyrosines on GHR/JAK. The availability of GHR on the cell surface is regulated by at least two processes; internalization and cleavage from the suface by metalloproteases.