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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1990-3-22
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pubmed:abstractText |
p21ras is palmitoylated on a cysteine residue near the C-terminus. Changing Cys-186 to Ser in oncogenic forms produces a non-palmitoylated protein that fails to associate with membranes and does not transform NIH 3T3 cells. To examine whether palmitate acts in a general way to increase ras protein hydrophobicity, or is involved in more specific interactions between p21ras and membranes, we constructed genes that encode non-palmitoylated ras proteins containing myristic acid at their N-termini. Myristoylated, activated ras, without palmitate (61Leu/186Ser) exhibited both efficient membrane association and full transforming activity. Unexpectedly, we found that myristoylated forms of normal cellular ras were also potently transforming. Myristoylated c-ras retained the high GTP binding and GTPase characteristic of the cellular protein and, moreover, bound predominantly GDP in vivo. This implied that it continued to interact with GAP (GTPase-activating protein). While the membrane binding induced by myristate permitted transformation, only palmitate produced a normal (non-transforming) association of ras with membranes and must therefore regulate ras function by some unique property that myristate does not mimic. Myristoylation thus represents a novel mechanism by which the ras proto-oncogene protein can become transforming.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0300-5127
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
867-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2695362-Acylation,
pubmed-meshheading:2695362-Animals,
pubmed-meshheading:2695362-Cell Line,
pubmed-meshheading:2695362-Cell Membrane,
pubmed-meshheading:2695362-Mice,
pubmed-meshheading:2695362-Myristates,
pubmed-meshheading:2695362-Myristic Acids,
pubmed-meshheading:2695362-Oncogene Protein p21(ras),
pubmed-meshheading:2695362-Palmitates
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pubmed:year |
1989
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pubmed:articleTitle |
Activation of cellular p21ras by myristoylation.
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pubmed:affiliation |
La Jolla Cancer Research Foundation, CA 92037.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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