IDENTIFICATION OF JAK2 AS A GROWTH-HORMONE RECEPTOR-ASSOCIATED TYROSINE KINASE

Growth hormone receptor (GHR) forms a complex with a tyrosine kinase, suggesting involvement of a ligand-activated tyrosine kinase in intrac ellular signaling by growth hormone (GH). Here we identify JAK2, a non receptor tyrosine kinase, as a GHR-associated tyrosine kinase. Immunol ogical approaches were used to establish GH-dependent complex formatio n between JAK2 and GHR, activation of JAK2 tyrosine kinase activity, a nd tyrosyl phosphorylation of both JAK2 and GHR. The JAK2-GHR and JAK2 -erythropoietin receptor interactions described here and in the accomp anying paper provide a molecular basis for involvement of tyrosyl phos phorylation in physiological responses to these ligands and suggest a shared signaling mechanism among members of the cytokine/hematopoietin receptor family.