Expression of receptor-like protein tyrosine phosphatase alpha in rat embryo fibroblasts activates mitogen-activated protein kinase and c-Jun.
Anti-c-Src and anti-phosphotyrosine immunoprecipitates from receptor-like protein tyrosine phosphatase alpha (PTP alpha)-transfected and control rat embryo fibroblasts contain a 39-kDa phosphoprotein (p39) whose phosphorylation is enhanced by PTP alpha expression. The p39 that co-immunoprecipitates with c-Src has been identified as c-Jun by immunological and functional criteria; it is recognized by several different anti-c-Jun antibodies and binds to a c-Jun recognition element-containing oligonucleotide. Whereas the association of c-Src and c-Jun is unexpected, it may be of significance in PTP alpha signaling since we have previously demonstrated that c-Src is activated by PTP alpha (Zheng, X. M., Wang, Y., and Pallen, C. J. (1992) Nature 359, 336-339. Examination of c-Jun activity in these fibroblasts demonstrates that c-Jun DNA binding activity and c-Jun-mediated transcription of a chloramphenicol acetyltransferase reporter gene are elevated in PTP alpha-expressing cells. In addition to c-Jun activation, mitogen-activated protein kinase is activated in PTP alpha-expressing cells and translocated to the nuclei of these cells. The nuclear localization of activated mitogen-activated protein kinase and c-Jun suggests that their activation represents downstream events in the receptor-like PTP alpha-initiated signaling pathway(s).
Zheng
X M
XM
Cell Regulation Laboratory, National University of Singapore.
Pallen
C J
CJ
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004622:Embryo, Mammalian / Q000201:enzymology*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D051381:Rats; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; D011956:Receptors, Cell Surface; D004247:DNA; D016392:Proto-Oncogene Proteins pp60(c-src); D017027:Protein Tyrosine Phosphatases; C516845:Ptpra protein, rat; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4