HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 13, 11520-11527, March 28, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/13/11520    most recent M211061200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, H. Articles by Cohen, D. M. Search for Related Content PubMed PubMed Citation Articles by Xu, H. Articles by Cohen, D. M. Social Bookmarking                      What's this?

Regulation of a Transient Receptor Potential (TRP) Channel by Tyrosine Phosphorylation
SRC FAMILY KINASE-DEPENDENT TYROSINE PHOSPHORYLATION OF TRPV4 ON TYR-253 MEDIATES ITS RESPONSE TO HYPOTONIC STRESS^*

Hongshi Xu, Hongyu Zhao, Wei Tian, Kiyotsugu Yoshida^§, Jean-Baptiste Roullet, and David M. Cohen^¶

From the  Division of Nephrology, Department of Medicine, and ^¶ Department of Cell and Developmental Biology, Oregon Health & Science University and the Portland Veterans Affairs Medical Center, Portland, Oregon 97201 and the ^§ Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

The recently identified transient receptor potential (TRP) channel family member, TRPV4 (formerly known as OTRPC4, VR-OAC, TRP12, and VRL-2) is activated by hypotonicity. It is highly expressed in the kidney as well as blood-brain barrier-deficient hypothalamic nuclei responsible for systemic osmosensing. Apart from its gating by hypotonicity, little is known about TRPV4 regulation. We observed that hypotonic stress resulted in rapid tyrosine phosphorylation of TRPV4 in a heterologous expression model and in native murine distal convoluted tubule cells in culture. This tyrosine phosphorylation was sensitive to the inhibitor of Src family tyrosine kinases, PP1, in a dose-dependent fashion. TRPV4 associated with Src family kinases by co-immunoprecipitation studies and confocal immunofluorescence microscopy, and this interaction required an intact Src family kinase SH2 domain. One of these kinases, Lyn, was activated by hypotonic stress and phosphorylated TRPV4 in an immune complex kinase assay and an in vitro kinase assay using recombinant Lyn and TRPV4. Transfection of wild-type Lyn dramatically potentiated hypotonicity-dependent TRPV4 tyrosine phosphorylation whereas dominant negative-acting Lyn modestly inhibited it. Through mutagenesis studies, the site of tonicity-dependent tyrosine phosphorylation was mapped to Tyr-253, which is conserved across all species from which TRPV4 has been cloned. Importantly, point mutation of Tyr-253 abolished hypotonicity-dependent channel activity. In aggregate, these data indicate that hypotonic stress results in Src family tyrosine kinase-dependent tyrosine phosphorylation of the tonicity sensor TRPV4 at residue Tyr-253 and that this residue is essential for channel function in this context. This is the first example of direct regulation of TRP channel function through tyrosine phosphorylation.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				W. E. B. Sipe, S. M. Brierley, C. M. Martin, B. D. Phillis, F. B. Cruz, E. F. Grady, W. Liedtke, D. M. Cohen, S. Vanner, L. A. Blackshaw, et al. Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1288 - G1298. [Abstract] [Full Text] [PDF]

				M.-Y. Jian, J. A. King, A.-B. Al-Mehdi, W. Liedtke, and M. I. Townsley High Vascular Pressure-Induced Lung Injury Requires P450 Epoxygenase-Dependent Activation of TRPV4 Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 386 - 392. [Abstract] [Full Text] [PDF]

				N. Alessandri-Haber, O. A. Dina, E. K. Joseph, D. B. Reichling, and J. D. Levine Interaction of Transient Receptor Potential Vanilloid 4, Integrin, and Src Tyrosine Kinase in Mechanical Hyperalgesia J. Neurosci., January 30, 2008; 28(5): 1046 - 1057. [Abstract] [Full Text] [PDF]

				L. Birder, F. A. Kullmann, H. Lee, S. Barrick, W. de Groat, A. Kanai, and M. Caterina Activation of Urothelial Transient Receptor Potential Vanilloid 4 by 4{alpha}-Phorbol 12,13-Didecanoate Contributes to Altered Bladder Reflexes in the Rat J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 227 - 235. [Abstract] [Full Text] [PDF]

				W. Zhang, Q. Tong, K. Conrad, J. Wozney, J. Y. Cheung, and B. A. Miller Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1 Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1746 - C1758. [Abstract] [Full Text] [PDF]

				W. Liedtke Hydromineral Neuroendocrinology: Role of TRPV ion channels in sensory transduction of osmotic stimuli in mammals Exp Physiol, May 1, 2007; 92(3): 507 - 512. [Abstract] [Full Text] [PDF]

				W. Liedtke Transient receptor potential vanilloid channels functioning in transduction of osmotic stimuli J. Endocrinol., December 1, 2006; 191(3): 515 - 523. [Abstract] [Full Text] [PDF]

				M. P. Cuajungco, C. Grimm, K. Oshima, D. D'hoedt, B. Nilius, A. R. Mensenkamp, R. J. M. Bindels, M. Plomann, and S. Heller PACSINs Bind to the TRPV4 Cation Channel: PACSIN 3 MODULATES THE SUBCELLULAR LOCALIZATION OF TRPV4 J. Biol. Chem., July 7, 2006; 281(27): 18753 - 18762. [Abstract] [Full Text] [PDF]

				H. Tsushima and M. Mori Antidipsogenic effects of a TRPV4 agonist, 4{alpha}-phorbol 12,13-didecanoate, injected into the cerebroventricle Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2006; 290(6): R1736 - R1741. [Abstract] [Full Text] [PDF]

				Y. Fu, A. Subramanya, D. Rozansky, and D. M. Cohen WNK kinases influence TRPV4 channel function and localization Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1305 - F1314. [Abstract] [Full Text] [PDF]

				H. Xu, Y. Fu, W. Tian, and D. M. Cohen Glycosylation of the osmoresponsive transient receptor potential channel TRPV4 on Asn-651 influences membrane trafficking Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1103 - F1109. [Abstract] [Full Text] [PDF]

				W. Tian, Y. Fu, D. H. Wang, and D. M. Cohen Regulation of TRPV1 by a novel renally expressed rat TRPV1 splice variant Am J Physiol Renal Physiol, January 1, 2006; 290(1): F117 - F126. [Abstract] [Full Text] [PDF]

				A. F. Odell, J. L. Scott, and D. F. Van Helden Epidermal Growth Factor Induces Tyrosine Phosphorylation, Membrane Insertion, and Activation of Transient Receptor Potential Channel 4 J. Biol. Chem., November 11, 2005; 280(45): 37974 - 37987. [Abstract] [Full Text] [PDF]

				X. Yao and C. J. Garland Recent Developments in Vascular Endothelial Cell Transient Receptor Potential Channels Circ. Res., October 28, 2005; 97(9): 853 - 863. [Abstract] [Full Text] [PDF]

				W. Liedtke TRPV4 plays an evolutionary conserved role in the transduction of osmotic and mechanical stimuli in live animals J. Physiol., August 15, 2005; 567(1): 53 - 58. [Abstract] [Full Text] [PDF]

				H. Xu, W. Tian, J. N. Lindsley, T. T. Oyama, J. M. Capasso, C. J. Rivard, H. T. Cohen, S. M. Bagnasco, S. Anderson, and D. M. Cohen EphA2: expression in the renal medulla and regulation by hypertonicity and urea stress in vitro and in vivo Am J Physiol Renal Physiol, April 1, 2005; 288(4): F855 - F866. [Abstract] [Full Text] [PDF]

				D. M. Cohen SRC family kinases in cell volume regulation Am J Physiol Cell Physiol, March 1, 2005; 288(3): C483 - C493. [Abstract] [Full Text] [PDF]

				L. D. Bozulic, W. L. Dean, and N. A. Delamere The Influence of SRC-Family Tyrosine Kinases on Na,K-ATPase Activity in Lens Epithelium Invest. Ophthalmol. Vis. Sci., February 1, 2005; 46(2): 618 - 622. [Abstract] [Full Text] [PDF]

				Z. Gong, W. Son, Y. Doo Chung, J. Kim, D. W. Shin, C. A. McClung, Y. Lee, H. W. Lee, D.-J. Chang, B.-K. Kaang, et al. Two Interdependent TRPV Channel Subunits, Inactive and Nanchung, Mediate Hearing in Drosophila J. Neurosci., October 13, 2004; 24(41): 9059 - 9066. [Abstract] [Full Text] [PDF]

				G. Vazquez, B. J. Wedel, B. T. Kawasaki, G. St. J. Bird, and J. W. Putney Jr. Obligatory Role of Src Kinase in the Signaling Mechanism for TRPC3 Cation Channels J. Biol. Chem., September 24, 2004; 279(39): 40521 - 40528. [Abstract] [Full Text] [PDF]

				X. Jin, N. Morsy, J. Winston, P. J. Pasricha, K. Garrett, and H. I. Akbarali Modulation of TRPV1 by nonreceptor tyrosine kinase, c-Src kinase Am J Physiol Cell Physiol, August 1, 2004; 287(2): C558 - C563. [Abstract] [Full Text] [PDF]

				W. Tian, M. Salanova, H. Xu, J. N. Lindsley, T. T. Oyama, S. Anderson, S. Bachmann, and D. M. Cohen Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments Am J Physiol Renal Physiol, July 1, 2004; 287(1): F17 - F24. [Abstract] [Full Text] [PDF]

				G. U. Ahmmed, D. Mehta, S. Vogel, M. Holinstat, B. C. Paria, C. Tiruppathi, and A. B. Malik Protein Kinase C{alpha} Phosphorylates the TRPC1 Channel and Regulates Store-operated Ca2+ Entry in Endothelial Cells J. Biol. Chem., May 14, 2004; 279(20): 20941 - 20949. [Abstract] [Full Text] [PDF]

				M.-K. Chung, H. Lee, A. Mizuno, M. Suzuki, and M. J. Caterina TRPV3 and TRPV4 Mediate Warmth-evoked Currents in Primary Mouse Keratinocytes J. Biol. Chem., May 14, 2004; 279(20): 21569 - 21575. [Abstract] [Full Text] [PDF]

				N. Alessandri-Haber, O. A. Dina, J. J. Yeh, C. A. Parada, D. B. Reichling, and J. D. Levine Transient Receptor Potential Vanilloid 4 Is Essential in Chemotherapy-Induced Neuropathic Pain in the Rat J. Neurosci., May 5, 2004; 24(18): 4444 - 4452. [Abstract] [Full Text] [PDF]

				L. J. Drew, D. K. Rohrer, M. P. Price, K. E. Blaver, D. A. Cockayne, P. Cesare, and J. N. Wood Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones J. Physiol., May 1, 2004; 556(3): 691 - 710. [Abstract] [Full Text] [PDF]

				C. Hisatsune, Y. Kuroda, K. Nakamura, T. Inoue, T. Nakamura, T. Michikawa, A. Mizutani, and K. Mikoshiba Regulation of TRPC6 Channel Activity by Tyrosine Phosphorylation J. Biol. Chem., April 30, 2004; 279(18): 18887 - 18894. [Abstract] [Full Text] [PDF]

				H.-Y. Kwan, Y. Huang, and X. Yao Regulation of canonical transient receptor potential isoform 3 (TRPC3) channel by protein kinase G PNAS, February 24, 2004; 101(8): 2625 - 2630. [Abstract] [Full Text] [PDF]

				B. Nilius, J. Vriens, J. Prenen, G. Droogmans, and T. Voets TRPV4 calcium entry channel: a paradigm for gating diversity Am J Physiol Cell Physiol, February 1, 2004; 286(2): C195 - C205. [Abstract] [Full Text] [PDF]

				J. Vriens, H. Watanabe, A. Janssens, G. Droogmans, T. Voets, and B. Nilius Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4 PNAS, January 6, 2004; 101(1): 396 - 401. [Abstract] [Full Text] [PDF]

				M. Suzuki, A. Hirao, and A. Mizuno Microfilament-associated Protein 7 Increases the Membrane Expression of Transient Receptor Potential Vanilloid 4 (TRPV4) J. Biol. Chem., December 19, 2003; 278(51): 51448 - 51453. [Abstract] [Full Text] [PDF]

				K. Muraki, Y. Iwata, Y. Katanosaka, T. Ito, S. Ohya, M. Shigekawa, and Y. Imaizumi TRPV2 Is a Component of Osmotically Sensitive Cation Channels in Murine Aortic Myocytes Circ. Res., October 31, 2003; 93(9): 829 - 838. [Abstract] [Full Text] [PDF]

				D. M. Cohen Of Rafts and Moving Water Sci. Signal., September 9, 2003; 2003(199): pe36 - pe36. [Abstract] [Full Text] [PDF]

				M.-K. Chung, H. Lee, and M. J. Caterina Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes J. Biol. Chem., August 22, 2003; 278(34): 32037 - 32046. [Abstract] [Full Text] [PDF]