Activation of a Novel Calcium-dependent Protein-tyrosine Kinase
| Autor: | Benjamin F. Calvo, Xiong Li, Matthias Wilm, Robert J. Anderegg, Lee M. Graves, Ruth Chen Dy, Deborah Hunter, H. Shelton Earp, Hong Yu, Thomas L. Dawson, Gail S. Marchetto |
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| Rok vydání: | 1996 |
| Předmět: |
MAP kinase kinase kinase
biology Cyclin-dependent kinase 2 Tyrosine phosphorylation Cell Biology Mitogen-activated protein kinase kinase Biochemistry Molecular biology Protein kinase R MAP2K7 Cell biology chemistry.chemical_compound chemistry biology.protein ASK1 Cyclin-dependent kinase 9 Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 271:29993-29998 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.47.29993 |
| Popis: | Many G protein-coupled receptors (e.g. that of angiotensin II) activate phospholipase Cβ, 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 p125FAK and both enzymes are expressed in WB and GN4 cells. Angiotensin II, which only slightly increases p125FAK 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 ∼ 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 5-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 TNFα) did not. In summary, cells expressing CADTK/PYK2 appear to have two alternative JNK activation pathways: one stress-activated and the other calcium-dependent. |
| Databáze: | OpenAIRE |
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