Activation and association of the Tec tyrosine kinase with the human prolactin receptor: mapping of a Tec/Vav1-receptor binding site.

Kline JB, Moore DJ, Clevenger CV
Mol Endocrinol. 2001 15 (5): 832-41

PMID: 11328862 · DOI:10.1210/mend.15.5.0631

Stimulation of the PRL receptor (PRLr) results in the activation of the guanine nucleotide exchange factor (GEF) p95Vav1 with corresponding alterations in cytoarchitecture and cell motility. To better understand the mechanisms involved in the regulation of Vav1 activity, the role of the tyrosine kinase p70Tec was examined. Coimmunoprecipitation and in vitro kinase assays revealed that ligand stimulation of the PRLr resulted in the rapid activation of Tec and its concomitant association with the PRLR: When coexpressed in COS-1 cells, both Vav1 and Tec were found to associate with the PRLr in the presence of ligand. In the absence of receptor, a constitutive complex between Vav1 and Tec was noted. Both Vav1 and Tec, however, were capable of independent engagement of a bipartite intracellular domain of the PRLR: Deletion mapping studies confined this interaction to residues 323 to 527 of the intracellular domain of the PRLR: Furthermore, Tec enhanced the GEF activity of Vav1 as evidenced by an increase in GTP-bound Rac1. These data would suggest a pivotal function for the formation of a Tec/Vav1/PRLr complex during PRL-driven signal transduction, given the role of Vav1 in the control of cell proliferation and the regulation of Rho family-mediated cytoskeletal alterations.

MeSH Terms (21)

3T3 Cells Animals Binding Sites Cell Cycle Proteins COS Cells Enzyme Activation Female Humans Ligands Mice Peptide Mapping Phosphorylation Precipitin Tests Protein-Tyrosine Kinases Protein Structure, Tertiary Proto-Oncogene Proteins Proto-Oncogene Proteins c-vav rac1 GTP-Binding Protein Receptors, Prolactin Recombinant Proteins Transfection

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