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Science 314 (5796): 122-125

Copyright © 2006 by the American Association for the Advancement of Science

Action of TFII-I Outside the Nucleus as an Inhibitor of Agonist-Induced Calcium Entry

Gabriela Caraveo,1 Damian B. van Rossum,2 Randen L. Patterson,2* Solomon H. Snyder,2,3,4 Stephen Desiderio1{dagger}

Abstract: TFII-I is a transcription factor and a target of phosphorylation by Bruton's tyrosine kinase. In humans, deletions spanning the TFII-I locus are associated with a cognitive defect, the Williams-Beuren cognitive profile. We report an unanticipated role of TFII-I outside the nucleus as a negative regulator of agonist-induced calcium entry (ACE) that suppresses surface accumulation of TRPC3 (transient receptor potential C3) channels. Inhibition of ACE by TFII-I requires phosphotyrosine residues that engage the SH2 (Src-homology 2) domains of phospholipase C–g (PLC-g) and an interrupted, pleckstrin homology (PH)–like domain that binds the split PH domain of PLC-g. Our observations suggest a model in which TFII-I suppresses ACE by competing with TRPC3 for binding to PLC-g.

1 Department of Molecular Biology and Genetics, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3 Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4 Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* Present address: Department of Biology, Pennsylvania State University, State College, PA 16802, USA.

{dagger} To whom correspondence should be addressed. E-mail: sdesider{at}jhmi.edu


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