This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taniyama, Y.
Right arrow Articles by Griendling, K. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taniyama, Y.
Right arrow Articles by Griendling, K. K.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*Protein
*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*L-TYROSINE

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2003, p. 8019-8029, Vol. 23, No. 22
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.22.8019-8029.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Pyk2- and Src-Dependent Tyrosine Phosphorylation of PDK1 Regulates Focal Adhesions

Yoshihiro Taniyama,1 David S. Weber,1 Petra Rocic,1 Lula Hilenski,1 Marjorie L. Akers,1 Jongsun Park,2 Brian A. Hemmings,2 R. Wayne Alexander,1 and Kathy K. Griendling1*

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322,1 Friedrich Miescher Institute, Basel CH-4058, Switzerland2

Received 19 February 2003/ Returned for modification 7 April 2003/ Accepted 13 August 2003

3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a signal integrator that activates the AGC superfamily of serine/threonine kinases. PDK1 is phosphorylated on tyrosine by oxidants, although its regulation by agonists that stimulate G-protein-coupled receptor signaling pathways and the physiological consequences of tyrosine phosphorylation in this setting have not been fully identified. We found that angiotensin II stimulates the tyrosine phosphorylation of PDK1 in vascular smooth muscle in a calcium- and c-Src-dependent manner. The calcium-activated tyrosine kinase Pyk2 acts as a scaffold for Src-dependent phosphorylation of PDK1 on Tyr9, which permits phosphorylation of Tyr373 and -376 by Src. This critical function of Pyk2 is further supported by the observation that Pyk2 and tyrosine-phosphorylated PDK1 colocalize in focal adhesions after angiotensin II stimulation. Importantly, infection of smooth muscle cells with a Tyr9 mutant of PDK1 inhibits angiotensin II-induced tyrosine phosphorylation of paxillin and focal adhesion formation. These observations identify a novel interaction between PDK1 and Pyk2 that regulates the integrity of focal adhesions, which are major compartments for integrating signals for cell growth, apoptosis, and migration.

* Corresponding author. Mailing address: Emory University, Division of Cardiology, 319 WMB, 1639 Pierce Dr., Atlanta, GA 30322. Phone: (404) 727-8386. Fax: (404) 727-3585. E-mail: kgriend{at}emory.edu.

Molecular and Cellular Biology, November 2003, p. 8019-8029, Vol. 23, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.22.8019-8029.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ying, W.-Z., Aaron, K., Sanders, P. W. (2008). Dietary Salt Activates an Endothelial Proline-Rich Tyrosine Kinase 2/c-Src/Phosphatidylinositol 3-Kinase Complex to Promote Endothelial Nitric Oxide Synthase Phosphorylation. Hypertension 52: 1134-1141 [Abstract] [Full Text]  
  • Block, K., Eid, A., Griendling, K. K., Lee, D.-Y., Wittrant, Y., Gorin, Y. (2008). Nox4 NAD(P)H Oxidase Mediates Src-dependent Tyrosine Phosphorylation of PDK-1 in Response to Angiotensin II: ROLE IN MESANGIAL CELL HYPERTROPHY AND FIBRONECTIN EXPRESSION. J. Biol. Chem. 283: 24061-24076 [Abstract] [Full Text]  
  • Klei, L. R., Barchowsky, A. (2008). Positive Signaling Interactions between Arsenic and Ethanol for Angiogenic Gene Induction in Human Microvascular Endothelial Cells. Toxicol Sci 102: 319-327 [Abstract] [Full Text]  
  • Yang, K.-J., Shin, S., Piao, L., Shin, E., Li, Y., Park, K. A., Byun, H. S., Won, M., Hong, J., Kweon, G. R., Hur, G. M., Seok, J. H., Chun, T., Brazil, D. P., Hemmings, B. A., Park, J. (2008). Regulation of 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) by Src Involves Tyrosine Phosphorylation of PDK1 and Src Homology 2 Domain Binding. J. Biol. Chem. 283: 1480-1491 [Abstract] [Full Text]  
  • Matsui, A., Okigaki, M., Amano, K., Adachi, Y., Jin, D., Takai, S., Yamashita, T., Kawashima, S., Kurihara, T., Miyazaki, M., Tateishi, K., Matsunaga, S., Katsume, A., Honshou, S., Takahashi, T., Matoba, S., Kusaba, T., Tatsumi, T., Matsubara, H. (2007). Central Role of Calcium-Dependent Tyrosine Kinase PYK2 in Endothelial Nitric Oxide Synthase Mediated Angiogenic Response and Vascular Function. Circulation 116: 1041-1051 [Abstract] [Full Text]  
  • Yang, W., Zhang, Y., Li, Y., Wu, Z., Zhu, D. (2007). Myostatin Induces Cyclin D1 Degradation to Cause Cell Cycle Arrest through a Phosphatidylinositol 3-Kinase/AKT/GSK-3beta Pathway and Is Antagonized by Insulin-like Growth Factor 1. J. Biol. Chem. 282: 3799-3808 [Abstract] [Full Text]  
  • Mehta, P. K., Griendling, K. K. (2007). Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am. J. Physiol. Cell Physiol. 292: C82-C97 [Abstract] [Full Text]  
  • Guo, J., Sabri, A., Elouardighi, H., Rybin, V., Steinberg, S. F. (2006). {alpha}1-Adrenergic Receptors Activate AKT via a Pyk2/PDK-1 Pathway That Is Tonically Inhibited by Novel Protein Kinase C Isoforms in Cardiomyocytes. Circ. Res. 99: 1367-1375 [Abstract] [Full Text]  
  • Burdick, A. D., Ivnitski-Steele, I. D., Lauer, F. T., Burchiel, S. W. (2006). PYK2 mediates anti-apoptotic AKT signaling in response to benzo[a]pyrene diol epoxide in mammary epithelial cells. Carcinogenesis 27: 2331-2340 [Abstract] [Full Text]  
  • Lyle, A. N., Griendling, K. K. (2006). Modulation of vascular smooth muscle signaling by reactive oxygen species.. Physiology 21: 269-280 [Abstract] [Full Text]  
  • Clempus, R. E., Griendling, K. K. (2006). Reactive oxygen species signaling in vascular smooth muscle cells. Cardiovasc Res 71: 216-225 [Abstract] [Full Text]  
  • Taniyama, Y., Hitomi, H., Shah, A., Alexander, R. W., Griendling, K. K. (2005). Mechanisms of Reactive Oxygen Species-Dependent Downregulation of Insulin Receptor Substrate-1 by Angiotensin II. Arterioscler. Thromb. Vasc. Bio. 25: 1142-1147 [Abstract] [Full Text]  
  • Taniyama, Y., Ushio-Fukai, M., Hitomi, H., Rocic, P., Kingsley, M. J., Pfahnl, C., Weber, D. S., Alexander, R. W., Griendling, K. K. (2004). Role of p38 MAPK and MAPKAPK-2 in angiotensin II-induced Akt activation in vascular smooth muscle cells. Am. J. Physiol. Cell Physiol. 287: C494-C499 [Abstract] [Full Text]  
  • Huang, C., Borchers, C. H., Schaller, M. D., Jacobson, K. (2004). Phosphorylation of paxillin by p38MAPK is involved in the neurite extension of PC-12 cells. JCB 164: 593-602 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»