A SINGLE PHOSPHOTYROSINE RESIDUE OF THE PROLACTIN RECEPTOR IS RESPONSIBLE FOR ACTIVATION OF GENE-TRANSCRIPTION

Members of the cytokine/growth bormone/prolactin (PRL) receptor superf amily are associated with cytoplasmic tyrosine kinases of the Jak fami ly. For the PRL receptor (PRLR), after PRL stimulation, both the kinas e Jak2 and the receptor undergo tyrosine phosphorylation. To assess th e role of tyrosine phosphorylation of the PRLR in signal transduction, several mutant forms of the PRLR in which various tyrosine residues w ere changed to phenylalanine were constructed and their functional pro perties were investigated. We identified a single tyrosine residue loc ated at the C terminus of the PRLR to be necessary for in vivo activat ion of PRL-responsive gene transcription. This clearly indicates that a phosphotyrosine residue in the cytoplasmic domain of a member of the cytokine/growth hormone/PRL receptor superfamily is directly involved in signal transduction.