|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
36
|
|
pubmed:dateCreated |
1994-10-4
|
|
pubmed:abstractText |
We have studied whether hSOS1, a mammalian guanine nucleotide exchange factors responsible for activating Ras in response to growth factor stimulation, requires post-translational processing of Ras proteins to promote guanine nucleotide exchange. Our results showed that full-length hSOS1 catalyzed guanine nucleotide exchange on prenylated K-Ras(4B) but with a much lower efficiency on unprocessed K-Ras(4B). The apparent Km of hSOS1 for prenylated K-Ras(4B) was 225 (+/- 25) nM with a Vmax of 0.7 (+/- 0.1) mmol/min/mmol. The activity of hSOS1 against unprocessed K-Ras(4B) was too low to measure Km and Vmax. Consistent with these observations, full-length hSOS1 formed a complex with nucleotide-depleted prenylated K-Ras(4B) but not with unprocessed K-Ras(4B). A geranylgeranylated mutant of K-Ras(4B) was an equally good substrate for hSOS1 as wild-type farnesylated K-Ras. Similarly hSOS1 promoted guanine nucleotide exchange on prenylated Ha-Ras but showed minimal activity toward unprocessed Ha-Ras. Neither the polybasic domain of K-Ras (4B) or palmitoylation of Ha-Ras were required for hSOS1-promoted guanine nucleotide exchange. We attempted to identify a minimal region of hSOS1 capable of promoting guanine nucleotide exchange on both prenylated and unprocessed K-Ras. However, a truncated form of hSOS1 comprising only the CDC25 homology domain retained preferential catalytic activity against prenylated K-Ras, whereas the cognate domain from CDC25 was more active against unprocessed K-Ras.
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
9
|
|
pubmed:volume |
269
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
22672-7
|
|
pubmed:dateRevised |
2007-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:8077219-Amino Acid Sequence,
pubmed-meshheading:8077219-Animals,
pubmed-meshheading:8077219-Cell Line,
pubmed-meshheading:8077219-Cloning, Molecular,
pubmed-meshheading:8077219-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:8077219-GTP-Binding Proteins,
pubmed-meshheading:8077219-Gene Expression,
pubmed-meshheading:8077219-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:8077219-Guanosine Diphosphate,
pubmed-meshheading:8077219-Kinetics,
pubmed-meshheading:8077219-Mammals,
pubmed-meshheading:8077219-Molecular Sequence Data,
pubmed-meshheading:8077219-Moths,
pubmed-meshheading:8077219-Palmitic Acid,
pubmed-meshheading:8077219-Palmitic Acids,
pubmed-meshheading:8077219-Polymerase Chain Reaction,
pubmed-meshheading:8077219-Protein Prenylation,
pubmed-meshheading:8077219-Protein Processing, Post-Translational,
pubmed-meshheading:8077219-Proteins,
pubmed-meshheading:8077219-Proto-Oncogene Proteins p21(ras),
pubmed-meshheading:8077219-Recombinant Proteins,
pubmed-meshheading:8077219-Transfection,
pubmed-meshheading:8077219-ras Guanine Nucleotide Exchange Factors
|
|
pubmed:year |
1994
|
|
pubmed:articleTitle |
Prenylation of Ras proteins is required for efficient hSOS1-promoted guanine nucleotide exchange.
|
|
pubmed:affiliation |
ONYX Pharmaceuticals, Richmond, California 94806.
|
|
pubmed:publicationType |
Journal Article,
Comparative Study
|
