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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Bradykinin / pharmacology
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Calcium / metabolism*
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Calcium Channels / metabolism*
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Cell Line
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Cell Membrane / metabolism
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Cytoplasm / metabolism
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Humans
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Models, Biological
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Molecular Sequence Data
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PC12 Cells
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Phospholipase C gamma / chemistry
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Phospholipase C gamma / metabolism*
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Phosphorylation
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Protein Binding
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Protein Structure, Tertiary
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Rats
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TRPC Cation Channels / metabolism*
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Transcription Factors, TFII / chemistry
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Transcription Factors, TFII / metabolism*
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Uridine Triphosphate / pharmacology
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src Homology Domains
Substances
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Calcium Channels
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GTF2I protein, human
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TRPC Cation Channels
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TRPC3 cation channel
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Transcription Factors, TFII
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Phospholipase C gamma
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Bradykinin
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Calcium
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Uridine Triphosphate