Linked Life Data

7622464

Source:http://linkedlifedata.com/resource/pubmed/id/7622464

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
1995-8-25
pubmed:abstractText
Herbimycin A is an ansamycin antibiotic isolated as an agent that reverses morphological transformation induced by v-src. Although herbimycin A is widely used as a tool for inhibiting multiple tyrosine protein kinases and tyrosine kinase-activated signal transduction, its mechanism of action is not well defined and includes a decrease in both tyrosine kinase protein levels and activity (Uehara, Y., Murakami, Y., Sugimoto, Y., and Mizuno, S. (1989) Cancer Res. 49, 780-785). We now show that herbimycin A induces a profound decrease in the total cellular activity of transmembrane tyrosine kinase receptors, such as insulin-like growth factor, insulin, and epidermal growth factor receptors. A substantial proportion of the in vivo inhibition could be explained by an increase in the rate of degradation. The enhanced degradation of insulin-like growth factor-insulin receptor was prevented by inhibitors of the 20S proteasome, whereas neither lysosomotropic agents nor general serine- and cysteine-protease inhibitors were active in preventing receptor degradation induced by herbimycin A. Moreover, in a temperature-sensitive mutant cell line defective in the E1-catalyzed activation of ubiquitin, herbimycin A treatment at the restrictive temperature did not result in the degradation of insulin receptor. These results suggest that herbimycin A represents a novel class of drug that targets the degradation of tyrosine kinases by the 20S proteasome. The ubiquitin dependence of this process indicates that this degradation of tyrosine kinases might involve the 20S proteasome as the proteolytic core of the ubiquitin-dependent 26S protease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16580-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Herbimycin A induces the 20 S proteasome- and ubiquitin-dependent degradation of receptor tyrosine kinases.
pubmed:affiliation
Cell Biology and Genetics Program, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't