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

Academic Article

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.
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    Digital Object Identifier (doi)

    Author List

  • Frank SJ; Yi W; Zhao Y; Goldsmith JF; Gilliland G; Jiang J; Sakai I; Kraft AS
  • Start Page

  • 14776
  • End Page

  • 14785
  • Volume

  • 270
  • Issue

  • 24