A single phosphotyrosine residue of the prolactin receptor is responsible for activation of gene transcription.
Members of the cytokine/growth hormone/prolactin (PRL) receptor superfamily are associated with cytoplasmic tyrosine kinases of the Jak family. For the PRL receptor (PRLR), after PRL stimulation, both the kinase Jak2 and the receptor undergo tyrosine phosphorylation. To assess the role of tyrosine phosphorylation of the PRLR in signal transduction, several mutant forms of the PRLR in which various tyrosine residues were changed to phenylalanine were constructed and their functional properties were investigated. We identified a single tyrosine residue located at the C terminus of the PRLR to be necessary for in vivo activation 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.
Lebrun
J J
JJ
Institut National de la Santé et de la Recherche Médicale Unite 344, Faculté de Médecine Necker, Paris, France.
Ali
S
S
Goffin
V
V
Ullrich
A
A
Kelly
P A
PA
D002364:Caseins / Q000096:biosynthesis / Q000235:genetics; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2; D008156:Luciferases / Q000096:biosynthesis; D019000:Phosphotyrosine; D011388:Prolactin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D002364:Caseins; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011388:Prolactin; D008156:Luciferases; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2