Identification of Grb4/Nckβ, a Src Homology 2 and 3 Domain-containing Adapter Protein Having Similar Binding and Biological Properties to Nck*
- From the Department of Biochemistry and Molocular Biology and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202
Abstract
Adapter proteins made up of Src homology (SH) domains mediate multiple cellular signaling events initiated by receptor protein tyrosine kinases. Here we report that Grb4 is an adapter protein closely related to but distinct from Nck that is made up of three SH3 domains and one SH2 domain. Northern analysis indicated that both genes are expressed in multiple tissues. Both Nck and Grb4 proteins could associate with receptor tyrosine kinases and the SH3-binding proteins PAK, Sos1, and PRK2, and they synergized with v-Abl and Sos to induce gene expression via the transcription factor Elk-1. Although neither protein was transforming on its own, both Nck and Grb4 cooperated with v-Abl to transform NIH 3T3 cells and influenced the morphology and anchorage-dependent growth of wild type Ras-transformed cells. Nck and Grb4 therefore appear to be functionally redundant.
Footnotes
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↵* This work was supported by American Cancer Society Grant RPG 97-007-01-BE, United States Public Health Service Grants CA63139 and P60 DK20542-16, and funds from the Grace M. Showalter Trust (to L. A. Q.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, 635 Barnhill Drive, MS-4053, Indiana University School of Medicine, Indianapolis, IN 46202. Tel.: 317-274-8550; Fax: 317-274-4686; E-mail: lquillia{at}iupui.edu.
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↵2 B. K. Kay, personal communication.
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↵3 L. E. Braverman and L. A. Quilliam, unpublished observations.
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↵4 A. D. Cox and L. A. Quilliam, unpublished observations.
- Abbreviations:
- R-PTK
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receptor protein tyrosine kinase
- SH
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Src homology domain
- GST
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glutathioneS-transferase
- ERK
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extracellular signal-regulated kinase
- EGF
-
epidermal growth factor
- PDGF
-
platelet-derived growth factor
- PAGE
-
polyacrylamide gel electrophoresis
- WT
-
wild type
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- Received July 16, 1998.
- Revision received December 2, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
