Growth hormone receptor (GHR) forms a complex with a tyrosine kinase, suggesting involvement of a ligand-activated tyrosine kinase in intracellular signaling by growth hormone (GH). Here we identify JAK2, a nonreceptor tyrosine kinase, as a GHR-associated tyrosine kinase. Immunological approaches were used to establish GH-dependent complex formation between JAK2 and GHR, activation of JAK2 tyrosine kinase activity, and tyrosyl phosphorylation of both JAK2 and GHR. The JAK2-GHR and JAK2-erythropoietin receptor interactions described here and in the accompanying paper provide a molecular basis for involvement of tyrosyl phosphorylation in physiological responses to these ligands and suggest a shared signaling mechanism among members of the cytokine/hematopoietin receptor family.
Bibliographical noteFunding Information:
L. S. A. and G. S. C. contributed equally to the work and should both be considered first authors. This work was supported in part by research grants from the National Institutes of Health to C. C.-S. (ROl-DK34171) J. N. I. (ROl-DK42932 and P30 CA21765), and C. Cepko @Cl-EY08084); a grant from the American Lebanese Syrian Associated Charities to J. N. I.; National Research Service Award postdoctoral fellowships from the National Institutes of Health to L. S. A. (1 F32-DK08737) and G. S. C. (lF32GM14099); and postdoctoral fellowships to X. Y. from the Helen Hay Whitney Foundation and the Medical Foundation/Charles King Trust. We thank Drs. R. Jove, J. Schwartz, M. Uhler. and C. Cepko for helpful comments,
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