J Biol Chem. 2005 Nov 11;280(45):37974-87. Epub 2005 Sep 6.
Epidermal growth factor induces tyrosine phosphorylation, membrane insertion, and activation of transient receptor potential channel 4.
Odell, A. F., Scott, J. L., Van Helden, D. F.,
["School of Biomedical Sciences, Level 5 MSB, University of Newcastle, Callaghan, New South Wales, Australia. adam.odell@newcastle.edu.au"]
["School of Biomedical Sciences, Level 5 MSB, University of Newcastle, Callaghan, New South Wales, Australia. adam.odell@newcastle.edu.au"]
Various members of the canonical family of transient receptor potential channels (TRPCs) exhibit increased cation influx following receptor stimulation or Ca(2+) 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 Ca(2+) 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.
PMID: 16144838

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Screening
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Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPC4 |
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FYN | Inference | Prediction | 16144838 | |||||
TRPC4 |
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LYN | Inference | Prediction | 16144838 | |||||
TRPC4 |
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SRC | Inference | Prediction | 16144838 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Validation: In vivo validation
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Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPC4 |
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FYN | Co-immunoprecipitation | COS-7 | 16144838 | |||||
TRPC4 |
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FYN | Co-immunoprecipitation | COS-7 | Human | Full-length | Not specifed | Full-length | 16144838 | |
TRPC4 |
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LYN | Co-immunoprecipitation | COS-7 | 16144838 | |||||
TRPC4 |
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LYN | Co-immunoprecipitation | COS-7 | Human | Full-length | Not specifed | Full-length | 16144838 | |
TRPC4 |
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NHERF1 | Co-immunofluorescence staining | COS-7 | Human | Full-length | Not specifed | Full-length | 16144838 | |
TRPC4 |
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NHERF1 | Co-immunoprecipitation | COS-7 | Human | Full-length | Not specifed | Full-length | 16144838 | |
TRPC4 |
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SRC | Co-immunoprecipitation | COS-7 | Human | Full-length | Not specifed | Full-length | 16144838 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
