JAK2 and STAT5, but not JAK1 and STAT1, are required for prolactin-induced beta-lactoglobulin transcription.
Several different Janus kinases (JAKs) and signal transducers and activation of transcription (STATs) have been implicated in mediating the biological responses induced by PRL, based on their ligand-dependent tyrosine phosphorylation and activation. However, these criteria alone do not prove that a particular JAK or STAT is essential for signal transduction. We have used mutant cell lines defective in JAK1, JAK2, or STAT1 to examine their roles in PRL-dependent signaling. JAK2 is absolutely required for PRL-dependent phosphorylation of the receptor, activation of STATs, and induction of beta-lactoglobulin. Wild type, but not kinase-negative JAK2, restores all responses to PRL in JAK2-defective cells, suggesting that JAK2 function, not merely the protein, is required. In contrast, JAK1, which is phosphorylated in response to PRL, is not required for any of these functions. Although STAT1 homodimers do form in response to PRL, no defect in PRL-dependent signaling is apparent when STAT1 is missing, suggesting that STAT5, which is strongly activated in response to PRL, is primarily responsible for driving the expression of PRL-responsive genes.
Han
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Y
Department of Molecular Biology, Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
Watling
D
D
Rogers
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NC
Stark
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GR
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D007782:Lactoglobulins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008894:Milk Proteins; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D007782:Lactoglobulins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014443:Tyrosine; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507905:Jak1 protein, mouse; C507926:Jak2 protein, mouse; D053613:Janus Kinase 1; D053614:Janus Kinase 2