The protein tyrosine kinase P59fyn is associated with prolactin (PRL) receptor and is activated by PRL stimulation of T-lymphocytes.
The clonal expansion of antigen-stimulated T-lymphocytes during an immune response is mediated by several lymphokines. Strong evidence now exists that the neuroendocrine hormone PRL is necessary, but not sufficient, for T-cell proliferation. Little is known, however, of the signal transduction mechanisms of the PRL receptor (PRLR) within T-cells. We demonstrate here that PRL stimulation of the T-cell line Nb2 induced the concentration- and time-dependent activation of the protein tyrosine kinase p59fyn, but not of four other src family protein tyrosine kinases. Activation of fyn was also observed in Concanavalin-A-primed peripheral blood lymphocytes stimulated with PRL and in Nb2 cells incubated with anti-PRLR antibodies. The activation of fyn by PRL stimulation correlated with Nb2 cell proliferation. Immunoblot analysis of anti-fyn and anti-PRLR immune complexes revealed an association between each PRLR isoform and p59fyn. These studies demonstrate for the first time an association between the PRLR and a src family protein tyrosine kinase affiliated with signal transduction.
Clevenger
C V
CV
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia 19104.
Medaglia
M V
MV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D016399:Lymphoma, T-Cell / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D010766:Phosphorylation; D011233:Precipitin Tests; D011388:Prolactin / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D051381:Rats; D011981:Receptors, Prolactin / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin; D003208:Concanavalin A; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn