Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor

S. J. Frank, W. Yi, Y. Zhao, J. F. Goldsmith, G. Gilliland, J. Jiang, I. Sakai, A. S. Kraft

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

Abstract

Growth hormone (GH) treatment of cells promotes activation of JAK2, a GH receptor (GHR)-associated tyrosine kinase. We now explore JAK2 regions required for GHR-induced signaling. Wild-type (WT) JAK2 and JAK2 molecules with deletions of the amino terminus (JAK2(ATD)), carboxyl terminus (JAK2(CTD)), or kinase-like domain (JAK2(PKD)) were each transiently coexpressed in COS-7 cells with the rabbit GHR. The following responses were assayed: GH-induced transactivation of a luciferase reporter governed by a c- fos enhancer element; GH-induced shift in the molecular mass of a cotransfected epitope-tagged extracellular signal-regulated kinase molecule; and GH-induced antiphosphotyrosine immunoprecipitability of the transfected JAK2 form. In each assay, WTJAK2 and JAK2(PKD) allowed GH-induced signaling, whereas JAK2(ATD) and JAK2(CTD) did not. Anti-GHR serum coimmunoprecipitated WTJAK2, JAK2(PKD), and JAK2(CTD), but not JAK2(ATD). Finally, a chimera in which the JAK2 kinase domain replaced the GHR cytoplasmic domain signaled GH- induced transactivation. We conclude: 1) kinase-like domain deletion eliminates neither physical nor functional interaction between JAK2 and the GHR; 2) kinase domain deletion eliminates functional but not physical coupling of JAK2 to the GHR; 3) interaction with the GHR appears dependent on the NH2-terminal one-fifth of JAK2; and 4) a GH-responsive signaling unit can include as little as the GHR external and transmembrane domains and the JAK2 kinase domain.

Original languageEnglish (US)
Pages (from-to)14776-14785
Number of pages10
JournalJournal of Biological Chemistry
Volume270
Issue number24
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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