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Prolactin Stimulates Phosphorylation of the Human T-Cell Antigen Receptor Complex and ZAP-70 Tyrosine Kinase: A Potential Mechanism for Its Immunomodulation

Departments of Surgery and Pharmacology, University of Arizona College of Medicine (D.W.M.), Tucson, Arizona 85724; Research Service, VA Medical Center (D.W.M.), Tucson, Arizona 85723; Department of Pharmacology and Toxicology, University of North Dakota School of Medicine & Health Sciences (J.S.K., A.R.B.), Grand Forks, North Dakota 58202

Address all correspondence and requests for reprints to: David W. Montgomery, Ph.D., VA Medical Center, Research Service, Department of Surgery, 3601 S. 6th Avenue, Tucson, Arizona 85723.

	Abstract

Top Abstract

 
Prolactin (PRL) is an immunomodulatory hormone which promotes T-cell activation and proliferation. However, the intracellular mechanisms of this action in normal lymphocytes are unknown. Because the PRL receptor (PRLR) activates several signals also activated by the T-cell antigen receptor (TCR)/CD3 complex, we evaluated whether signaling "cross-talk" occurs between these distinct receptors. Using human thymocytes, human peripheral blood lymphocytes and the rat Nb2 lymphoma T-cell, we found that PRL induced rapid phosphorylation of multiple, TCR/CD3 complex proteins, an event required for lymphocyte activation. Two of these phosphorylated proteins were identified to be CD3 epsilon and ZAP-70 tyrosine kinase, molecules essential for TCR function. Further, PRL induced tyrosyl phosphorylation of ZAP-70 in each population of T-lymphocytes tested, demonstrating for the first time that ZAP-70 is a target of PRL action. Taken together, our results suggest that the PRLR directly affects T-lymphocyte activation by means of signaling cross-talk with the TCR/CD3 complex.

Received August 8, 1997.

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This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Montgomery, D. W. Articles by Buckley, A. R. Search for Related Content PubMed PubMed Citation Articles by Montgomery, D. W. Articles by Buckley, A. R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB L-TYROSINE