PARTICIPATION OF JAK AND STAT PROTEINS IN GROWTH HORMONE-INDUCED SIGNALING

The binding of growth hormone leads to dimerization of its receptor, a ccompanied by phosphorylation and activation of intracellular tyrosine kinases (JAKs) and the latent cytoplasmic transcriptions factors STAT 1, STAT3, and STAT5. Both JAK1 and JAK2 are phosphorylated in response to growth hormone in mouse 3T3 F442A and human HT1080 cells. The role s of JAKs in growth hormone signal transduction were examined by using mutant HT1080 cells missing either JAK1 or JAK2. JAK2 is absolutely r equired for growth hormone-dependent phosphorylation of the receptor, STAT1 and STAT3, JAK1, and the SH2-containing adaptor molecule Shc. In contrast, JAK1 is not required for any of the above functions. These data indicate that JAK2 is both necessary and sufficient for the growt h hormone-dependent phosphorylation events required to couple the rece ptor both to STAT-dependent signaling pathways and to pathways involvi ng She. Furthermore, STATE is activated by growth hormone in 3T3 F442A cells, but not in HT1080 cells, revealing that the set of STATs activ ated by growth hormone can vary, possibly contributing to the specific ity of the growth hormone response in different cell types.