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Molecular and Cellular Biology, February 2004, p. 1736-1746, Vol. 24, No. 4
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.4.1736-1746.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human CNK1 Acts as a Scaffold Protein, Linking Rho and Ras Signal Transduction Pathways

Aron B. Jaffe,1 Pontus Aspenström,2 and Alan Hall1*

MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom,1 Ludwig Institute for Cancer Research, S-751 24 Uppsala, Sweden2

Received 9 April 2003/ Returned for modification 22 May 2003/ Accepted 17 November 2003

Rho family GTPases act as molecular switches to control a variety of cellular responses, including cytoskeletal rearrangements, changes in gene expression, and cell transformation. In the active, GTP-bound state, Rho interacts with an ever-growing number of effector molecules, which promote distinct biochemical pathways. Here, we describe the isolation of hCNK1, the human homologue of Drosophila connector enhancer of ksr, as an effector for Rho. hCNK1 contains several protein-protein interaction domains, and Rho interacts with one of these, the PH domain, in a GTP-dependent manner. A mutant hCNK1, which is unable to bind to Rho, or depletion of endogenous hCNK1 by using RNA interference inhibits Rho-induced gene expression via serum response factor but has no apparent effect on Rho-induced stress fiber formation, suggesting that it acts as a specific effector for transcriptional, but not cytoskeletal, activation pathways. Finally, hCNK1 associates with Rhophilin and RalGDS, Rho and Ras effector molecules, respectively, suggesting that it acts as a scaffold protein to mediate cross talk between the two pathways.

* Corresponding author. Mailing address: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom. Phone: 44 020 7679 7806. Fax: 44 020 7679 7805. E-mail: alan.hall{at}ucl.ac.uk.

Molecular and Cellular Biology, February 2004, p. 1736-1746, Vol. 24, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.4.1736-1746.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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