A 40-amino acid segment of the growth hormone receptor cytoplasmic domain is essential for GH-induced tyrosine-phosphorylated cytosolic proteins.

It has become evident that intracellular protein phosphorylation plays an important role in mediating signal transduction of hormones and growth factors, including growth hormone (GH). We have previously demonstrated that GH can stimulate tyrosine phosphorylation of cellular proteins with approximate molecular masses of 95,000 daltons (pp95) in GH-treated 3T3-F442A preadipocytes and in mouse L cells that express recombinant porcine or bovine GH receptors. In the present study, a series of GH receptor (GHR) truncation analogs were constructed and examined for their abilities to induce pp95. The results revealed that a region of approximately 40 amino acids in the porcine GHR cytoplasmic domain is essential for induction of pp95. The results also established that the 115 amino acids (517-638) near the C terminus of porcine GHR are not required for pp95 induction. Moreover, the basal levels of GH-induced pp95 in parental mouse L cells was suppressed by expression of these GHR truncation analogs. This suggests that pp95 induced by GH may be mediated by GHR dimerization and can be inhibited by overexpression of truncated porcine GHRs.