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doi: 10.1242/10.1242/jcs.00207

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Journal of Cell Science 115, 4915-4924 (2002)
doi: 10.1242/jcs.00207

Research Article

Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway-mediated Rap1 activation

Akira Sakakibara1,*,§, Yusuke Ohba2, Kazuo Kurokawa2, Michiyuki Matsuda2 and Seisuke Hattori1,{ddagger}

1 Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan
2 Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
* Present address: Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA
{ddagger} Present address: Division of Cellular Proteomics, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

§ Author for correspondence (e-mail: as6by{at}virginia.edu)

Accepted 3 October 2002

Chat (Cas/HEF1-associated signal transducer) is a novel signaling molecule with an N-terminal SH2 domain and C-terminal Cas/HEF1 association domain that is implicated in the regulation of cell adhesion. The Cas/HEF1 association domain also shows sequence similarity with guanine nucleotide exchange factors for Ras family small GTPases. In this study, we found significant activation of Rap1 in Chat-overexpressing cells. Myr-Chat, a membrane-targeted form of Chat, activated Rap1 more efficiently. Interestingly, Chat and Cas synergistically activated Rap1. Certain Cas, Crk or C3G mutants suppressed Rap1 activation by Chat. We also confirmed the ternary complex formation consisting of Chat, Cas and Crk. Thus, it is likely that Chat-induced Rap1 activation was mediated by upregulation of the Cas-Crk-C3G signaling pathway rather than direct guanine nucleotide exchange factor activity of Chat. We further demonstrated that Myr-Chat expression induced cell periphery spreading and cell shape branching and that this activity also depended on the Cas-Crk-C3G pathway and Rap1 activity. Moreover, expression of Myr-Chat enhanced integrin-mediated cell adhesion. Taken together we propose a novel role for the Chat-Cas complex in controlling cell adhesion via the activation of Rap1.

Key words: Cas, Cell adhesion, Chat, Guanine nucleotide exchange factor, Rap1, Small GTPase






© The Company of Biologists Ltd 2002