PROLACTIN RECRUITS STAT1, STAT3 AND STAT5 INDEPENDENT OF CONSERVED RECEPTOR TYROSINES TYR402, TYR479, TYR515 AND TYR580

The present study of prolactin (PRL) receptor-mediated recruitment of signal transducers and activators of transcription (STATs) demonstrate s that PRL activates STAT3, in addition to STAT1 and STAT5 as previous ly reported, and that STAT1, STAT3 and STAT5 are mediators of PRL effe cts in cells whether of lymphoid, myeloid or mammary epithelial origin . Furthermore, receptor mutants M240 and T280 that do not mediate PRL- induced JAK2 activation and cell proliferation, are also unable to med iate STAT activation, supporting the proposed model of JAK2 as the ini tial effector protein used by PRL receptors. On the other hand, tyrosi ne phosphorylation analysis and electrophoretic mobility shift assays showed that receptor mutant G328, which lacks four of the five conserv ed cytoplasmic tyrosine residues of PRL receptors, retained the abilit y to activate JAK2 and STAT1, STAT3 and STAT5. These results support t he notion that phosphotyrosyl residues other than those of the recepto r, i.e., JAK2, are involved in recruiting STAT proteins to the activat ed PRL receptor complex.