https://scholars.lib.ntu.edu.tw/handle/123456789/473869
標題: | The Tumor Suppressor DAPK Is Reciprocally Regulated by Tyrosine Kinase Src and Phosphatase LAR | 作者: | Wang W.-J. Kuo J.-C. Ku W. Lee Y.-R. Lin F.-C. YIH-LEONG CHANG Lin Y.-M. Chen C.-H. Huang Y.-P. Chiang M.-J. Yeh S.-W. Wu P.-R. Shen C.-H. CHEN-TU WU Chen R.-H. |
公開日期: | 2007 | 卷: | 27 | 期: | 5 | 起(迄)頁: | 701-716 | 來源出版物: | Molecular Cell | 摘要: | Death-associated protein kinase (DAPK) is a calmodulin-regulated serine/threonine kinase and elicits tumor suppression function through inhibiting cell adhesion/migration and promoting apoptosis. Despite these biological functions, the signaling mechanisms through which DAPK is regulated remain largely elusive. Here, we show that the leukocyte common antigen-related (LAR) tyrosine phosphatase dephosphorylates DAPK at pY491/492 to stimulate the catalytic, proapoptotic, and antiadhesion/antimigration activities of DAPK. Conversely, Src phosphorylates DAPK at Y491/492, which induces DAPK intra-/intermolecular interaction and inactivation. Upon EGF stimulation, a rapid Src activation leads to subsequent LAR downregulation, and these two events act in synergism to inactivate DAPK, thereby facilitating tumor cell migration and invasion toward EGF. Finally, DAPK Y491/492 hyperphosphorylation is found in human cancers in which Src activity is aberrantly elevated. These results identify LAR and Src as a DAPK regulator through their reciprocal modification of DAPK Y491/492 residues and establish a functional link of this DAPK-regulatory circuit to tumor progression. ? 2007 Elsevier Inc. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-34548249520&doi=10.1016%2fj.molcel.2007.06.037&partnerID=40&md5=73b82ed317c111691d7f66ea7ec463ea https://scholars.lib.ntu.edu.tw/handle/123456789/473869 |
ISSN: | 1097-2765 | DOI: | 10.1016/j.molcel.2007.06.037 | SDG/關鍵字: | CD45 antigen; death associated protein kinase; phosphatase; protein tyrosine kinase; small interfering RNA; tumor suppressor protein; tyrosine kinase src; unclassified drug; amino acid sequence; animal cell; apoptosis; article; cancer inhibition; catabolism; cell adhesion; cell differentiation; cell growth; controlled study; dephosphorylation; enzyme activation; enzyme activity; enzyme assay; enzyme regulation; human; human cell; immunoblotting; in vitro study; in vivo study; leukocyte migration inhibition test; nonhuman; protein expression; protein function; protein phosphorylation; protein protein interaction; signal transduction; tumor cell; Apoptosis Regulatory Proteins; Calcium-Calmodulin-Dependent Protein Kinases; Cell Line, Tumor; Epidermal Growth Factor; Humans; Neoplasms; Nerve Tissue Proteins; Phosphorylation; Protein Tyrosine Phosphatases; Proto-Oncogene Proteins pp60(c-src); Receptor-Like Protein Tyrosine Phosphatases, Class 2; Receptors, Cell Surface; Signal Transduction; Tumor Suppressor Proteins |
顯示於: | 病理學科所 |
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