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Molecular and Cellular Biology, May 2002, p. 3230-3236, Vol. 22, No. 10
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.10.3230-3236.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Grap Negatively Regulates T-Cell Receptor-Elicited Lymphocyte Proliferation and Interleukin-2 Induction

Randy Shen,1,2 Ying-Bin Ouyang,2,{dagger} Cheng-Kui Qu,2,{ddagger} Andres Alonso,3 Lindsey Sperzel,3 Tomas Mustelin,3 Mark H. Kaplan,2,4 and Gen-Sheng Feng3*

Program in Signal Transduction Research, The Burnham Institute, La Jolla, California 92037,3 Departments of Biochemistry and Molecular Biologyof,1 Microbiology and Immunology,4 Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 462022

Received 28 November 2001/ Returned for modification 24 January 2002/ Accepted 21 February 2002

Grb-2-related adaptor protein (Grap) is a Grb2-like SH3-SH2-SH3 adaptor protein with expression restricted to lymphoid tissues. Grap-/- lymphocytes isolated from targeted Grap-deficient mice exhibited enhanced proliferation, interleukin-2 production, and c-fos induction in response to mitogenic T-cell receptor (TCR) stimulation, compared to wild-type cells. Ectopic expression of Grap led to a suppression of Elk-1-directed transcription induced by the Ras/Erk pathway, without having effects on gene expression mediated by Jnk and p38 mitogen-activated protein kinases. Together, these data suggest that Grap, unlike Grb2, acts as a negative regulator of TCR-stimulated intracellular signaling by downregulating signal relay through the Ras/Erk pathway.

* Corresponding author. Mailing address: The Burnham Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 713-6265. Fax: (858) 713-6274. E-mail: gfeng{at}burnham.org.

{dagger} Present address: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.

{ddagger} Present address: American Red Cross, Rockville, MD 20855.

Molecular and Cellular Biology, May 2002, p. 3230-3236, Vol. 22, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.10.3230-3236.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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