PROLACTIN STIMULATES PHOSPHORYLATION OF THE HUMAN T-CELL ANTIGEN RECEPTOR COMPLEX AND ZAP-70 TYROSINE KINASE - A POTENTIAL MECHANISM FOR ITS IMMUNOMODULATION

Prolactin (PRL) is an immunomodulatory hormone which promotes T-cell a ctivation and proliferation. However, the intracellular mechanisms of this action in normal lymphocytes are unknown. Because the PRL recepto r (PRLR) activates several signals also activated by the T-cell antige n receptor (TCR)/CD3 complex, we evaluated whether signaling ''cross-t alk'' occurs between these distinct receptors. Using human thymocytes, human peripheral blood lymphocytes and the rat Nb2 lymphoma T-cell, w e found that PRL induced rapid phosphorylation of multiple, TCR/CD3 co mplex proteins, an event required for lymphocyte activation. Two of th ese 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-lym phocytes tested, demonstrating for the first time that ZAP-70 is a tar get of PRL action. Taken together, our results suggest that the PRLR d irectly affects T-lymphocyte activation by means of signaling cross-ta lk with the TCR/CD3 complex.