Activation of a novel calcium-dependent protein-tyrosine kinase - Correlation with c-jun N-terminal kinase but not mitogen-activated protein kinase activation

被引:243
作者
Yu, H
Li, X
Marchetto, GS
Dy, R
Hunter, D
Calvo, B
Dawson, TL
Wilm, M
Anderegg, RJ
Graves, LM
Earp, HS
机构
[1] UNIV N CAROLINA,SCH MED,LINEBERGER COMPREHENS CANC CTR,DEPT MED,CHAPEL HILL,NC 27599
[2] UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27599
[3] EUROPEAN MOL BIOL LAB,PROT & PEPTIDE GRP,D-69012 HEIDELBERG,GERMANY
[4] GLAXO WELLCOME INC,RES & DEV,RES TRIANGLE PK,NC 27709
关键词
D O I
10.1074/jbc.271.47.29993
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Many G protein-coupled receptors (e.g. that of angiotensin II) activate phospholipase C beta, initially increasing intracellular calcium and activating protein kinase C. In the WB and GN4 rat liver epithelial cell lines, agonist-induced calcium signals also stimulate tyrosine phosphorylation and subsequently increase the activity of c-Jun N-terminal kinase (JNK), We have now purified the major calcium-dependent tyrosine kinase (CADTK), and by peptide and nucleic acid sequencing identified it as a rat homologue of human PYK2. CADTK/PYK2 is most closely related to p125(FAK) and both enzymes are expressed in WE and GN4 cells, Angiotensin II, which only slightly increases p125(FAK) tyrosine phosphorylation in GN4 cells, substantially increased CADTK tyrosine autophosphorylation and kinase activity, Agonists for other G protein-coupled receptors (e.g. LPA), or those increasing intracellular calcium (thapsigargin), also stimulated CADTK. In comparing the two rat liver cell lines, GN4 cells exhibited similar to 5-fold greater angiotensin II- and thapsigargin-dependent CADTK activation than WB cells, Although maximal JNK activation by stress-dependent pathways (e.g. UV and anisomycin) was equivalent in the two cell lines, calcium-dependent JNK activation was B-fold greater in GN4, correlating with CADTK activation. In contrast to JNK, the thapsigargin-dependent calcium signal did not activate mitogen-activated protein kinase and Ang II-dependent mitogen-activated protein kinase activation was not correlated with CADTK activation. Finally, while some stress-dependent activators of the JNK pathway (NaCl and sorbitol) stimulated CADTK, others (anisomycin, UV, and TNF alpha) did not, In summary, cells expressing CADTK/PYK2 appear to have two alternative JNK activation pathways: one stress-activated and the other calcium-dependent.
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收藏
页码:29993 / 29998
页数:6
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