Stimulation of c-Src by prolactin is independent of Jak2.
Interaction of prolactin (PRL) with its receptor (PRLR) leads to activation of Jak and Src family tyrosine kinases. The PRL/growth hormone/cytokine receptor family conserves a proline-rich sequence in the cytoplasmic juxtamembrane region (Box 1) required for association and subsequent activation of Jaks. In the present work, we studied the mechanisms underlying c-Src kinase activation by PRL and the role that Jak2 plays in this process. PRL addition to chicken embryo fibroblasts (CEF) expressing the rat PRLR long form resulted in activation of c-Src and Jak2 and in tyrosine phosphorylation of the receptor. Receptor phosphorylation was due to associated Jak2, since in cells expressing either a Box 1 mutated PRLR (PRLR(4P-A)), which is unable to interact with Jak2, or a kinase-domain-deleted Jak2 (Jak2Deltak), PRL did not stimulate receptor phosphorylation. Interestingly, addition of PRL to cells expressing PRLR(4P-A) resulted in an activation of c-Src equivalent to that observed with the wild-type receptor. These findings indicate that PRL-mediated stimulation of c-Src was independent of Jak2 activation and of receptor phosphorylation. Our results suggest that PRL-activated Src could send signals to downstream cellular targets independently of Jak2.
Fresno Vara
J A
JA
Instituto de Investigaciones Biomédicas, C.S.I.C., Arturo Duperier 4, 28029 Madrid, Spain.
Carretero
M V
MV
Gerónimo
H
H
Ballmer-Hofer
K
K
Martín-Pérez
J
J
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002642:Chick Embryo; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D053614:Janus Kinase 2; D009154:Mutation; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin; D014443:Tyrosine; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D019061:src-Family Kinases