Modulation of TRPV1 by nonreceptor tyrosine kinase, c-Src kinase.
The capsaicin receptor TRPV1 is a nonselective cation channel that is expressed in sensory neurons. In this study, we examined the role of the nonreceptor cellular tyrosine kinase c-Src kinase in the modulation of the rat TRPV1. Capsaicin-induced currents in identified colonic dorsal root ganglion neurons were blocked by the c-Src kinase inhibitor PP2 and enhanced by the tyrosine phosphatase inhibitor sodium orthovandate. PP2 also abolished currents in human embryonic kidney-293 cells transfected with rat TRPV1, whereas cotransfection of TRPV1 with v-Src resulted in fivefold increase in capsaicin-induced currents. In cells transfected with dominant-negative c-Src and TRPV1, capsaicin-induced currents were decreased by approximately fourfold. TRPV1 co-immunoprecipitated with Src kinase and was tyrosine phosphorylated. These studies demonstrate that TRPV1 is a potential target for cellular tyrosine kinase-dependent phosphorylation.
Jin
Xiaochun
X
Dept. of Physiology, University of Oklahoma Health Science Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA.
Morsy
Nemat
N
Winston
John
J
Pasricha
Pankaj J
PJ
Garrett
Kennon
K
Akbarali
Hamid I
HI
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D007668:Kidney / Q000166:cytology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000201:enzymology*; D009619:Nociceptors / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D019061:src-Family Kinases
D011955:Receptors, Drug; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D002211:Capsaicin