Prolactin stimulates phosphorylation of the human T-cell antigen receptor complex and ZAP-70 tyrosine kinase: a potential mechanism for its immunomodulation

Endocrinology
D W MontgomeryA R Buckley

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.

Citations

Oct 7, 2015·Nature Reviews. Endocrinology·Wilson SavinoMireille Dardenne
Nov 28, 2001·Lupus·D W Montgomery
Nov 28, 2001·Lupus·C V Clevenger, J B Kline
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Jun 6, 2003·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Flora IppolitiTullio Frediani
Mar 28, 2001·Annals of the New York Academy of Sciences·A R Buckley, D J Buckley
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Aug 11, 2021·Translational Oncology·Kuan-Hui Ethan ChenAmeae M Walker

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