GROWTH-HORMONE (GH)-INDUCED TYROSINE-PHOSPHORYLATED PROTEINS IN CELLSTHAT EXPRESS GH RECEPTORS

We have shown previously that growth hormone (GH)-induced tyrosine pho sphorylation of a 95-kDa protein in mouse L-cells stably transfected w ith the GH receptor. In addition to induction of pp95, we have establi shed that GH also induces tyrosine phosphorylation of a 42-kDa protein and a 130-kDa protein, as detected with phosphotyrosine antibodies. A time course of tyrosine phosphorylation on GH treatment indicates tha t within the GH signal transduction cascade, tyrosine phosphorylation of pp95 occurs by 1 min, whereas tyrosine phosphorylation of pp42 was not detected until 5 min. Additionally, the concentration of GH needed to stimulate tyrosine phosphorylation of pp42 was greater than that r equired for pp95. The pp42 protein comigrates with a 42-kDa protein id entified as extracellular signal-regulated kinase 2 (ERK2). Growth fac tors, such as FGF, PDGF, IGF-I, and insulin, induce tyrosine phosphory lation of pp42 in pGHR-W10 cells and in 3T3-F442A preadipocytes; howev er, they are unable to induce pp95. These results suggest that GH indu ction of tyrosine-phosphorylated pp42 may represent a common signal tr ansduction point of various growth factors, including GH, whereas tyro sine phosphorylation of pp95 is GH specific.