PTP1D IS A POSITIVE REGULATOR OF THE PROLACTIN SIGNAL LEADING TO BETA-CASEIN PROMOTER ACTIVATION

Stimulation of the prolactin receptor (PRLR), a member of the cytokine /growth hormone receptor family, results in activation of the associat ed Jak2 tyrosine kinase and downstream signaling pathways. We report t hat PTP1D, a cytoplasmic protein tyrosine phosphatase containing two S rc homology 2 (SH2) domains, physically associates with the PRLR-Jak2 complex and is tyrosine-phosphorylated upon stimulation with prolactin . The formation of the trimeric PRLR-Jak2-PTP1D complex is critical fo r transmission of a lactogenic signal, while PTP1D phosphorylation is necessary, but not sufficient. The dominant negative inhibitory effect of a phosphatase-deficient mutant on expression of a beta-casein prom oter-controlled reporter gene is evidence for an essential role of ful ly functional PTP1D in the regulation of milk protein gene transcripti on.