Publication Date:
1994-05-13
Description:
Growth factor receptor-bound protein 2 (Grb2) links tyrosine-phosphorylated proteins to a guanine nucleotide releasing factor of the son of sevenless (Sos) class by attaching to the former by its Src homology 2 (SH2) moiety and to the latter by its SH3 domains. An isoform of grb2 complementary DNA (cDNA) was cloned that has a deletion in the SH2 domain. The protein encoded by this cDNA, Grb3-3, did not bind to phosphorylated epidermal growth factor receptor (EGFR) but retained functional SH3 domains and inhibited EGF-induced transactivation of a Ras-responsive element. The messenger RNA encoding Grb3-3 was expressed in high amounts in the thymus of rats at an age when massive negative selection of thymocytes occurs. Microinjection of Grb3-3 into Swiss 3T3 fibroblasts induced apoptosis. These findings indicate that Grb3-3, by acting as a dominant negative protein over Grb2 and by suppressing proliferative signals, may trigger active programmed cell death.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fath, I -- Schweighoffer, F -- Rey, I -- Multon, M C -- Boiziau, J -- Duchesne, M -- Tocque, B -- New York, N.Y. -- Science. 1994 May 13;264(5161):971-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rhone-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8178156" target="_blank"〉PubMed〈/a〉
Keywords:
3T3 Cells
;
*Adaptor Proteins, Signal Transducing
;
Amino Acid Sequence
;
Animals
;
*Apoptosis
;
Base Sequence
;
Cloning, Molecular
;
Epidermal Growth Factor/pharmacology
;
GRB2 Adaptor Protein
;
Humans
;
Mice
;
Molecular Sequence Data
;
Proteins/*genetics/metabolism
;
RNA, Messenger/genetics/metabolism
;
Rats
;
Receptor, Epidermal Growth Factor/*metabolism
;
T-Lymphocytes/cytology
;
Thymus Gland/metabolism
;
Transcriptional Activation/drug effects
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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