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J. Biol. Chem., Vol. 278, Issue 25, 22396-22403, June 20, 2003
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Linking the T Cell Surface Protein CD2 to the Actin-capping Protein CAPZ via CMS and CIN85*
**
From the
Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom and the ¶Ludwig Institute for Cancer Research, University College Branch of Cell and Molecular Biology, Royal Free and University College Medical School, London W1W 7BS, United Kingdom
Recruitment of CD2 to the immunological synapse in response to antigen is dependent on its proline-rich cytoplasmic tail. A peptide from this region (CD2:322–339) isolated CMS (human CD2AP); a related protein, CIN85; and the actin capping protein, CAPZ from a T cell line. In BIAcoreTM analyses, the N-terminal SH3 domains of CMS and CIN85 bound CD2:322–339 with similar dissociation constants (KD = 
100 µM). CAPZ bound the C-terminal half of CMS and CIN85. Direct binding between CMS/CIN85 and CAPZ provides a link with the actin cytoskeleton. Overexpression of a fragment from the C-terminal half or the N-terminal SH3 domain of CD2AP in a mouse T cell hybridoma resulted in enhanced interleukin-2 production and reduced T cell receptor down-modulation in response to antigen. These adaptor proteins are important in T cell signaling consistent with a role for CD2 in regulating pathways initiated by CMS/CIN85 and CAPZ.
Received for publication, March 12, 2003
* This work was supported by the Medical Research Council. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Present address: Everest Biotech. Ltd, Littlemore Park, Oxford OX4 4SS, UK.
|| Present address: Dept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94143-0446.
** To whom correspondence should be addressed: Sir William Dunn School of Pathology, South Parks Rd., Oxford OX1 3RE, UK. Tel.: 01865-275595; Fax: 01865-275591; E-mail: Marion.Brown{at}path.ox.ac.uk.
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