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Human CNK1 acts as a scaffold protein, linking Rho and Ras signal transduction pathways
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
2004 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 24, no 4, 1736-1746 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2004. Vol. 24, no 4, 1736-1746 p.
Keyword [en]
Adaptor Proteins; Signal Transducing, Animals, COS Cells, Carrier Proteins/chemistry/genetics/*metabolism, Drosophila Proteins, Hela Cells, Humans, Mutation; Missense, Oncogene Protein p21(ras)/*metabolism, Protein Binding, Protein Structure; Tertiary, Protein-Serine-Threonine Kinases/metabolism, Research Support; Non-U.S. Gov't, Sequence Deletion, Serum Response Factor/metabolism, Signal Transduction, Stress Fibers/metabolism, Transcription; Genetic, ral Guanine Nucleotide Exchange Factor/metabolism, rho GTP-Binding Proteins/*metabolism, rhoA GTP-Binding Protein/metabolism
National Category
Medical and Health Sciences Natural Sciences
URN: urn:nbn:se:uu:diva-73076DOI: 10.1128/MCB.24.4.1736-1746.2004PubMedID: 14749388OAI: oai:DiVA.org:uu-73076DiVA: diva2:100987
Available from: 2005-05-31 Created: 2005-05-31 Last updated: 2013-11-01Bibliographically approved

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