Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase

LS Argetsinger, GS Campbell, X Yang, BA Witthuhn… - Cell, 1993 - cell.com
LS Argetsinger, GS Campbell, X Yang, BA Witthuhn, O Silvennoinen, JN Ihle, C Carter-Su
Cell, 1993cell.com
Growth hormone receptor (GHR) forms a complex with a tyrosine kinase, suggesting
involvement of a ligandactivated 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 OH-dependent complex
formation between JAK2 and GHR, activation of JAW tyrosine kinase activity, and tyrosyl
phosphorylation of both JAK2 and GHR. The JAK2-GHR and JAK2-erythropoietin receptor …
Summary
Growth hormone receptor (GHR) forms a complex with a tyrosine kinase, suggesting involvement of a ligandactivated 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 OH-dependent complex formation between JAK2 and GHR, activation of JAW 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.
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