ABSTRACT

Shc protein is tyrosine phosphorylated upon B cell receptor (BCR) activation and after its phosphorylation interacts with the adaptor protein Grb2. In turn, Grb2 interacts with the guanine nucleotide exchange factor for Ras, mSOS. Several protein-tyrosine kinases (PTKs) participate in BCR signaling. However, it is not clear which PTK is involved in the phosphorylation of Shc, resulting in coupling to the Ras pathway. Tyrosine phosphorylation of Shc and its association with Grb2 were profoundly reduced in both Lyn- and Syk-deficient B cells upon BCR stimulation. Furthermore, kinase activity of these PTKs was required for phosphorylation of Shc. Shc interacted with Syk in B cells. This interaction and the requirement of Syk kinase activity for phosphorylation of Shc were also demonstrated by cotransfection in COS cells. Because Lyn is required for activation of Syk upon receptor stimulation, our results suggest that the Lyn-activated Syk phosphorylates Shc during BCR signaling.

FOOTNOTES

*

This work was supported in part by a grant-in-aid from the International Scientific Research Program of the Ministry of Education, Science, and Culture, Japan (to H. Y.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked ``advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§

To whom correspondence should be addressed: Dept. of Cardiovascular Molecular Biology, Bldg. 200, Rm. 4611, Lederle Laboratories, 401 North Middletown Rd., Pearl River, NY 10965. Tel.: 914-732-4814; Fax: 914-732-5665.

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The abbreviations used are: BCR, B cell receptor; PTK, protein-tyrosine kinase; SH, Src homology; mAb, monoclonal antibody; Ab, antibody.

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M. Takata and T. Kurosaki, manuscript in preparation.

()

T. Kurosaki, S. A. Johnson, L. Pao, K. Sada, H. Yamamura, and J. C. Cambier, submitted for publication.

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