Ligand binding and dimerization of the growth hormone (GH) receptor leads to the rapid tyrosine phosphorylation of the intracellular kinase, Jak2, to the tyrosine phosphorylation and activation of STAT protein(s) and to the tyrosine phosphorylation of the receptor itself. Expression of the human GH receptor in the mouse promyeloid, interleukin-3-dependent cell line, FDC-P1, shows that this receptor can signal ligand-dependent proliferation in these cells as well as induce the tyrosine phosphorylation of Jak2 and the activation of transcription factors. We now examine the requirement for tyrosine phosphorylation of the GH receptor for these three events by expression of a receptor without tyrosine residues in the intracellular domain. Six of the seven intracellular tyrosine residues were removed by a carboxyl-terminal truncation, and the remaining tyrosine was changed to phenylalanine to yield the GH receptor D351Stop/Y314F. When expressed in FDC-P1 cells, this receptor retained its ability to induce the tyrosine phosphorylation of Jak2, to induce the activation of transcription factors, and to signal ligand-dependent cell proliferation. Thus, tyrosine phosphorylation of the GH receptor is not essential for the signaling of these three events at least in this system. This finding contrasts with that for the interferon- receptor system where data indicate that the specific tyrosine phosphorylation of the interferon- receptor leads to an association with the STAT protein, p91, that is the mechanism by which ligand couples the receptor to the signal transduction system.

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