Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/25314

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Title
Epidermal growth factor induces tyrosine phosphorylation, membrane insertion, and activation of transient receptor potential channel 4
Author/Creator
Odell, Adam F.;  Scott, Judith L.;  van Helden, Dirk F.
Description
Various members of the canonical family of transient receptor potential channels (TRPCs) exhibit increased cation influx following receptor stimulation or Ca2+ store depletion. Tyrosine phosphorylation of TRP family members also results in increased channel activity; however, the link between the two events is unclear. We report that two tyrosine residues in the C terminus of human TRPC4 (hTRPC4), Tyr-959 and Tyr-972, are phosphorylated following epidermal growth factor (EGF) receptor stimulation of COS-7 cells. This phosphorylation was mediated by Src family tyrosine kinases (STKs), with Fyn appearing to be the dominant kinase. In addition, EGF receptor stimulation induced the exocytotic insertion of hTRPC4 into the plasma membrane dependent on the activity of STKs and was accompanied by a phosphorylation-dependent increase in the association of hTRPC4 with Na+/H+ exchanger regulatory factor. Furthermore, this translocation and association was defective upon mutation of Tyr-959 and Tyr-972 to phenylalanine. Significantly, inhibition of STKs was concomitant with a reduction in Ca2+ influx in both native COS-7 cells and hTRPC4-expressing HEK293 cells, with cells expressing the Y959F/Y972F mutant exhibiting a reduced EGF response. These findings represent the first demonstration of a mechanism for phosphorylation to modulate TRPC channel function.
Relation
Journal of Biological Chemistry Vol. 280, no. 45, p. 37974-37987
Date
2005
Publisher
American Society of Biological Chemists
Keyword(s)
exchanger regulatory factor;  operated ca2+ entry;  surface expression;  plasma-membrane;  cation channels;  trpc6 channel;  calcium-entry;  pdz-domain;  protein;  cells
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/25314
Identifier
ISSN:0021-9258
Language
eng
Reviewed
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Subject
"Journal of Biological Chemistry"
 
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