Action of TFII-I outside the nucleus as an inhibitor of agonist-induced calcium entry.
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.
Caraveo
Gabriela
G
Department of Molecular Biology and Genetics, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
van Rossum
Damian B
DB
Patterson
Randen L
RL
Snyder
Solomon H
SH
Desiderio
Stephen
S
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D016716:PC12 Cells; D051966:Phospholipase C gamma / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D050052:TRPC Cation Channels / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000737:chemistry / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000494:pharmacology; D018909:src Homology Domains
D015220:Calcium Channels; C104259:GTF2I protein, human; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D019473:Transcription Factors, TFII; D051966:Phospholipase C gamma; D001920:Bradykinin; D002118:Calcium; D014544:Uridine Triphosphate