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| THE SH2 AND SH3 DOMAIN CONTAINING PROTEIN GRB2 LINKS RECEPTOR TYROSINE KINASES TO RAS SIGNALING |
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| Author(s): LOWENSTEIN EJ, DALY RJ, BATZER AG, LI W, MARGOLIS B, LAMMERS R, ULLRICH A, SKOLNIK EY, BARSAGI D, SCHLESSINGER J |
| Source: CELL Volume: 70 Issue: 3 Pages: 431-442 Published: AUG 7 1992 |
| Times Cited: 1,225 References: 56 |
| Abstract: A cDNA clone encoding a novel, widely expressed protein (called growth factor receptor-bound protein 2 or GRB2) containing one src homology 2 (SH2) domain and two SH3 domains was isolated. Immunoblotting experiments indicate that GRB2 associates with tyrosine-phosphorylated epidermal growth factor receptors (EGFRs) and platelet-derived growth factor receptors (PDGFRs) via its SH2 domain. Interestingly, GRB2 exhibits striking structural and functional homology to the C. elegans protein sem-5. It has been shown that sem-5 and two other genes called let-23 (EGFR like) and let-60 (ras like) lie along the same signal transduction pathway controlling C. elegans vulval induction. To examine whether GRB2 is also a component of ras signaling in mammalian cells, microinjection studies were performed. While injection of GRB2 or H-ras proteins alone into quiescent rat fibroblasts did not have mitogenic effect, microinjection of GRB2 together with H-ras protein stimulated DNA synthesis. These results suggest that GRB2/sem-5 plays a crucial role in a highly conserved mechanism for growth factor control of ras signaling. |
| Document Type: Article |
| Language: English |
| Reprint Address: LOWENSTEIN, EJ (reprint author), NYU MED CTR, DEPT PHARMACOL, NEW YORK, NY 10016 USA |
Addresses:
1. MAX PLANCK INST BIOCHEM, W-8033 MARTINSRIED, GERMANY
2. COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY 11724 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: JH124 |
| ISSN: 0092-8674 |
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