| Although growth hormone (GH) has been demonstrated to be an important regulator of body growth, cellular differentiation and metabolism, the mechanisms of intracellular signal transduction initiated by GH are unclear. This study investigates whether the cloned liver GH receptor (GHR) forms a complex with a cellular tyrosine kinase and if so, whether activation of this kinase is important in GH signaling and actions.;To determine whether the cloned liver GHR associates with a tyrosine kinase and can be tyrosyl phosphorylated by this kinase, the ability of ;A 121-kDa phosphoprotein (pp121) has been identified in this study as a candidate for the GHR-associated tyrosine kinase. pp121, which does not appear to bind to GH, is present in kinase-active anti-GH antibody immunoprecipitates from CHO cells expressing the cloned liver GH receptor, suggesting that pp121 forms a complex with GHR. Both GHR and pp121 are phosphorylated on tyrosyl residues in an in vitro kinase assay and in intact cells incubated with GH.;Regions of the GHR necessary for association and/or activation of the GHR-associated tyrosine kinase and tyrosyl phosphorylation of the GHR were determined using two GHR truncation mutants. When expressed in CHO and RIN5-AH cells, GHR... |
