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PMID: 7512734 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 8 ·1994-04-12 ·Pages 3443-7

Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M, Matuoka K, Takenawa T, Kurata T, Nagashima K

Abstract

CRK protein, together with GRB2/ASH and Nck proteins, belongs to the adaptor-type Src homology (SH)2-containing molecules, which transduce signals from tyrosine kinases. Here another guanine nucleotide-releasing protein (GNRP), C3G, has been identified as a CRK SH3-binding protein. The nucleotide sequence of a 4.1-kb C3G cDNA contains a 3.2-kb open reading frame encoding a 121-kDa protein, and antibodies against C3G have been shown to detect a protein of 130-140 kDa. The carboxyl terminus of C3G has a peptide sequence homologous to GNRPs for Ras, and the expression of this carboxyl terminus region suppresses the loss of CDC25 function in the yeast Saccharomyces cerevisiae. The C3G protein expressed in Escherichia coli binds to CRK and GRB2/ASH proteins. Mutational analysis of C3G assigns the SH3 binding region to a 50-amino acid region containing a proline-rich sequence. The mRNAs of both the C3G and CRK proteins are expressed ubiquitously in human adult and fetal tissues. The results of these studies suggest that the complex of CRK and C3G, or GRB2/ASH and C3G, may transduce the signals from tyrosine kinases to Ras in a number of different tissues.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Binding Sites Cloning, Molecular DNA, Complementary/genetics GRB2 Adaptor Protein Gene Expression Genetic Complementation Test Guanine Nucleotide Exchange Factors Humans Molecular Sequence Data Protein Binding Proteins/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-crk Proto-Oncogene Proteins pp60(c-src)/chemistry RNA, Messenger/genetics Sequence Alignment Sequence Homology, Amino Acid Signal Transduction ras Guanine Nucleotide Exchange Factors
Chemicals
Adaptor Proteins, Signal Transducing DNA, Complementary GRB2 Adaptor Protein GRB2 protein, human Guanine Nucleotide Exchange Factors Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-crk RNA, Messenger ras Guanine Nucleotide Exchange Factors Proto-Oncogene Proteins pp60(c-src)
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Tanaka S
Department of Pathology, School of Medicine, Hokkaido University, Sapporo, Japan.
Morishita T
Hashimoto Y
Hattori S
Nakamura S
Shibuya M
Matuoka K
Takenawa T
Kurata T
Nagashima K
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36 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.8.3443
Published
1994-04-12
Pages
3443-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43593
Subset
IM
Databases
GENBANK
D21239
External Links
PubMed source DOI: 10.1073/pnas.91.8.3443 PMC Full Text View journal details
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