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

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Science  06 Oct 2006:
Vol. 314, Issue 5796, pp. 122-125
DOI: 10.1126/science.1127815

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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.

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