| Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases. | |
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MedLine Citation:
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PMID: 17656313 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Methionine aminopeptidases (MetAPs) remove the N-terminal initiator methionine during protein synthesis, a prerequisite step for N-terminal myristoylation. N-myristoylation of proto-oncogene c-Src is essential for its membrane association and proper signal transduction. We used bengamides, a family of general MetAP inhibitors, to understand the downstream physiological functions of MetAPs. c-Src from bengamide A-treated cells retained its N-terminal methionine and suffered a decrease in N-terminal myristoylation, which was accompanied by a shift of its subcellular distribution from the plasma membrane to the cytosol. Furthermore, bengamide A decreased the tyrosine kinase activities of c-Src both in vitro and in vivo and eventually delayed cell-cycle progression through G(2)/M. Thus, c-Src is a physiologically relevant substrate for MetAPs whose dysfunction is likely to account for the cell-cycle effects of MetAP inhibitors including bengamide A. |
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Authors:
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Xiaoyi Hu; Yongjun Dang; Karen Tenney; Phillip Crews; Chiawei W Tsai; Katherine M Sixt; Philip A Cole; Jun O Liu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemistry & biology Volume: 14 ISSN: 1074-5521 ISO Abbreviation: Chem. Biol. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-07-27 Completed Date: 2007-12-13 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 9500160 Medline TA: Chem Biol Country: England |
Other Details:
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Languages: eng Pagination: 764-74 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Molecular Sciences, The Johns Hopkins University, School of Medicine, 725 N. Wolfe Street Baltimore, MD 21205, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aminopeptidases
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antagonists & inhibitors* Animals Azepines / pharmacology* Cell Line Humans Protease Inhibitors / pharmacology* Proto-Oncogene Proteins pp60(c-src) / metabolism Subcellular Fractions / enzymology, metabolism src-Family Kinases / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA047135/CA/NCI NIH HHS; CA052955/CA/NCI NIH HHS; CA074305/CA/NCI NIH HHS; CA1078743/CA/NCI NIH HHS; R01 CA078743-15/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Azepines; 0/Protease Inhibitors; EC 2.7.10.2/Proto-Oncogene Proteins pp60(c-src); EC 2.7.10.2/src-Family Kinases; EC 3.4.11.-/Aminopeptidases; EC 3.4.11.18/methionyl aminopeptidase |
| Comments/Corrections | |
Comment In:
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Chem Biol. 2007 Jul;14(7):732-4
[PMID:
17656307
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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