CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

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 arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ruest, P. J.
Right arrow Articles by Hanks, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ruest, P. J.
Right arrow Articles by Hanks, S. K.
Cell Growth & Differentiation Vol. 11, 41-48, January 2000
© 2000 American Association for Cancer Research


Articles

Phosphospecific Antibodies Reveal Focal Adhesion Kinase Activation Loop Phosphorylation in Nascent and Mature Focal Adhesions and Requirement for the Autophosphorylation Site1

Paul J. Ruest, Shyamali Roy, Ergang Shi, Raymond L. Mernaugh and Steven K. Hanks2

Departments of Cell Biology [P. J. R., S. R., S. K. H.] Biochemistry [R. L. M.], and The Vanderbilt-Ingram Cancer Center [E. S., R. L. M., S. K. H], Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Abstract

Focal adhesion kinase (FAK) is a key signaling molecule regulating cellular responses to integrin-mediated adhesion. Integrin engagement promotes FAK phosphorylation at multiple sites to achieve full FAK activation. Phosphorylation of FAK Tyr-397 creates a binding site for Src-family kinases, and phosphorylation of FAK Tyr-576/Tyr-577 in the kinase domain activation loop enhances catalytic activity. Using novel phosphospecific antibody reagents, we show that FAK activation loop phosphorylation is significantly elevated in cells expressing activated Src and is an early event following cell adhesion to fibronectin. In both cases, this regulation is largely dependent on Tyr-397. We also show that the FAK activation loop tyrosines are required for maximal Tyr-397 phosphorylation. Finally, immunostaining analyses revealed that tyrosine-phosphorylated forms of FAK are present in both newly forming and mature focal adhesions. Our findings support a model for reciprocal activation of FAK and Src-family kinases and suggest that FAK/Src signaling may occur during both focal adhesion assembly and turnover.




This article has been cited by other articles:


Home page
Mol. Cell. Biol.Home page
S. Y. S. Cheng, G. Sun, D. D. Schlaepfer, and C. J. Pallen
Grb2 Promotes Integrin-Induced Focal Adhesion Kinase (FAK) Autophosphorylation and Directs the Phosphorylation of Protein Tyrosine Phosphatase {alpha} by the Src-FAK Kinase Complex
Mol. Cell. Biol., February 1, 2014; 34(3): 348 - 361.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
E. Papusheva, F. M. de Queiroz, J. Dalous, Y. Han, A. Esposito, E. A. Jares-Erijmanxa, T. M. Jovin, and G. Bunt
Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility
J. Cell Sci., March 1, 2009; 122(5): 656 - 666.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
E. Ciccimaro, S. K. Hanks, and I. A. Blair
Quantification of Focal Adhesion Kinase Activation Loop Phosphorylation as a Biomarker of Src Activity
Mol. Pharmacol., March 1, 2009; 75(3): 658 - 666.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
A. Sabri, K. Rafiq, R. Seqqat, M. A. Kolpakov, R. Dillon, and L. J. Dell'italia
Sympathetic Activation Causes Focal Adhesion Signaling Alteration in Early Compensated Volume Overload Attributable to Isolated Mitral Regurgitation in the Dog
Circ. Res., May 9, 2008; 102(9): 1127 - 1136.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
X. Cai, D. Lietha, D. F. Ceccarelli, A. V. Karginov, Z. Rajfur, K. Jacobson, K. M. Hahn, M. J. Eck, and M. D. Schaller
Spatial and Temporal Regulation of Focal Adhesion Kinase Activity in Living Cells
Mol. Cell. Biol., January 1, 2008; 28(1): 201 - 214.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
F. Chang, C. A. Lemmon, D. Park, and L. H. Romer
FAK Potentiates Rac1 Activation and Localization to Matrix Adhesion Sites: A Role for betaPIX
Mol. Biol. Cell, January 1, 2007; 18(1): 253 - 264.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Khare, C. Holgren, and A. M. Samarel
Deoxycholic acid differentially regulates focal adhesion kinase phosphorylation: role of tyrosine phosphatase ShP2
Am J Physiol Gastrointest Liver Physiol, November 7, 2006; 291(6): G1100 - G1112.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
K. Rafiq, M. A. Kolpakov, M. Abdelfettah, D. N. Streblow, A. Hassid, L. J. Dell'Italia, and A. Sabri
Role of Protein-tyrosine Phosphatase SHP2 in Focal Adhesion Kinase Down-regulation during Neutrophil Cathepsin G-induced Cardiomyocytes Anoikis
J. Biol. Chem., July 14, 2006; 281(28): 19781 - 19792.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. Chen, S. C. Chen, and C. J. Pallen
Integrin-induced Tyrosine Phosphorylation of Protein-tyrosine Phosphatase-{alpha} Is Required for Cytoskeletal Reorganization and Cell Migration
J. Biol. Chem., April 28, 2006; 281(17): 11972 - 11980.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. Holinstat, N. Knezevic, M. Broman, A. M. Samarel, A. B. Malik, and D. Mehta
Suppression of RhoA Activity by Focal Adhesion Kinase-induced Activation of p190RhoGAP: ROLE IN REGULATION OF ENDOTHELIAL PERMEABILITY
J. Biol. Chem., January 27, 2006; 281(4): 2296 - 2305.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
A. Hamadi, M. Bouali, M. Dontenwill, H. Stoeckel, K. Takeda, and P. Ronde
Regulation of focal adhesion dynamics and disassembly by phosphorylation of FAK at tyrosine 397
J. Cell Sci., October 1, 2005; 118(19): 4415 - 4425.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
N. P.Y. Lee, D. D. Mruk, C.-h. Wong, and C. Y. Cheng
Regulation of Sertoli-Germ Cell Adherens Junction Dynamics in the Testis Via the Nitric Oxide Synthase (NOS)/cGMP/Protein Kinase G (PRKG)/{beta}-Catenin (CATNB) Signaling Pathway: An In Vitro and In Vivo Study
Biol Reprod, September 1, 2005; 73(3): 458 - 471.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
A. Polykratis, P. Katsoris, J. Courty, and E. Papadimitriou
Characterization of Heparin Affin Regulatory Peptide Signaling in Human Endothelial Cells
J. Biol. Chem., June 10, 2005; 280(23): 22454 - 22461.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
G. P. van Nieuw Amerongen, K. Natarajan, G. Yin, R. J. Hoefen, M. Osawa, J. Haendeler, A.J. Ridley, K. Fujiwara, V. W.M. van Hinsbergh, and B. C. Berk
GIT1 Mediates Thrombin Signaling in Endothelial Cells: Role in Turnover of RhoA-Type Focal Adhesions
Circ. Res., April 30, 2004; 94(8): 1041 - 1049.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
I. Hunger-Glaser, E. P. Salazar, J. Sinnett-Smith, and E. Rozengurt
Bombesin, Lysophosphatidic Acid, and Epidermal Growth Factor Rapidly Stimulate Focal Adhesion Kinase Phosphorylation at Ser-910: REQUIREMENT FOR ERK ACTIVATION
J. Biol. Chem., June 13, 2003; 278(25): 22631 - 22643.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
K. A. Hotchkiss, A. W. Ashton, and E. L. Schwartz
Thymidine Phosphorylase and 2-Deoxyribose Stimulate Human Endothelial Cell Migration by Specific Activation of the Integrins {alpha}5{beta}1 and {alpha}V{beta}3
J. Biol. Chem., May 23, 2003; 278(21): 19272 - 19279.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
A. Pace, L. J. Garcia-Marin, J. A. Tapia, M. J. Bragado, and R. T. Jensen
Phosphospecific Site Tyrosine Phosphorylation of p125FAK and Proline-rich Kinase 2 Is Differentially Regulated by Cholecystokinin Receptor Type A Activation in Pancreatic Acini
J. Biol. Chem., May 23, 2003; 278(21): 19008 - 19016.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
H. Mao, F. Li, K. Ruchalski, D. D. Mosser, J. H. Schwartz, Y. Wang, and S. C. Borkan
hsp72 Inhibits Focal Adhesion Kinase Degradation in ATP-depleted Renal Epithelial Cells
J. Biol. Chem., May 16, 2003; 278(20): 18214 - 18220.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
L. Kwong, M. A. Wozniak, A. S. Collins, S. D. Wilson, and P. J. Keely
R-Ras Promotes Focal Adhesion Formation through Focal Adhesion Kinase and p130Cas by a Novel Mechanism That Differs from Integrins
Mol. Cell. Biol., February 1, 2003; 23(3): 933 - 949.
[Abstract] [Full Text] [PDF]


Home page
JCBHome page
L. Zeng, X. Si, W.-P. Yu, H. T. Le, K. P. Ng, R. M.H. Teng, K. Ryan, D. Z.-M. Wang, S. Ponniah, and C. J. Pallen
PTP{alpha} regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration
J. Cell Biol., January 6, 2003; 160(1): 137 - 146.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
M. Toutant, A. Costa, J.-M. Studler, G. Kadare, M. Carnaud, and J.-A. Girault
Alternative Splicing Controls the Mechanisms of FAK Autophosphorylation
Mol. Cell. Biol., November 15, 2002; 22(22): 7731 - 7743.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
T. Akagi, K. Murata, T. Shishido, and H. Hanafusa
v-Crk Activates the Phosphoinositide 3-Kinase/AKT Pathway by Utilizing Focal Adhesion Kinase and H-Ras
Mol. Cell. Biol., October 15, 2002; 22(20): 7015 - 7023.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
L. A. Cary, R. A. Klinghoffer, C. Sachsenmaier, and J. A. Cooper
Src Catalytic but Not Scaffolding Function Is Needed for Integrin-Regulated Tyrosine Phosphorylation, Cell Migration, and Cell Spreading
Mol. Cell. Biol., April 15, 2002; 22(8): 2427 - 2440.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
P. J. Ruest, N.-Y. Shin, T. R. Polte, X. Zhang, and S. K. Hanks
Mechanisms of CAS Substrate Domain Tyrosine Phosphorylation by FAK and Src
Mol. Cell. Biol., November 15, 2001; 21(22): 7641 - 7652.
[Abstract] [Full Text] [PDF]


Home page
JCBHome page
K. A. West, H. Zhang, M. C. Brown, S. N. Nikolopoulos, M.C. Riedy, A. F. Horwitz, and C. E. Turner
The LD4 motif of paxillin regulates cell spreading and motility through an interaction with paxillin kinase linker (PKL)
J. Cell Biol., July 9, 2001; 154(1): 161 - 176.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
E. P. Salazar and E. Rozengurt
Src Family Kinases Are Required for Integrin-mediated but Not for G Protein-coupled Receptor Stimulation of Focal Adhesion Kinase Autophosphorylation at Tyr-397
J. Biol. Chem., May 25, 2001; 276(21): 17788 - 17795.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. Achison, C. M. Elton, P. G. Hargreaves, C. G. Knight, M. J. Barnes, and R. W. Farndale
Integrin-independent Tyrosine Phosphorylation of p125fak in Human Platelets Stimulated by Collagen
J. Biol. Chem., February 2, 2001; 276(5): 3167 - 3174.
[Abstract] [Full Text] [PDF]


Home page
JCBHome page
C. K. Klingbeil, C. R. Hauck, D. A. Hsia, K.C. Jones, S. R. Reider, and D. D. Schlaepfer
Targeting Pyk2 to {beta}1-Integrin-Containing Focal Contacts Rescues Fibronectin-Stimulated Signaling and Haptotactic Motility Defects of Focal Adhesion Kinase-Null Cells
J. Cell Biol., January 8, 2001; 152(1): 97 - 110.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
D. Vial, H. Okazaki, and R. P. Siraganian
The NH2-terminal Region of Focal Adhesion Kinase Reconstitutes High Affinity IgE Receptor-induced Secretion in Mast Cells
J. Biol. Chem., September 8, 2000; 275(36): 28269 - 28275.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
D. Vial, H. Okazaki, and R. P Siraganian
The NH2 terminal region of FAK reconstitutes high affinity IgE receptor induced secretion in mast cells
J. Biol. Chem., June 20, 2000; (2000) 2842200.
[Abstract]


Home page
J Biol ChemHome page
M. Achison, C. M. Elton, P. G. Hargreaves, C. G. Knight, M. J. Barnes, and R. W. Farndale
Integrin-independent Tyrosine Phosphorylation of p125fak in Human Platelets Stimulated by Collagen
J. Biol. Chem., February 2, 2001; 276(5): 3167 - 3174.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
E. P. Salazar and E. Rozengurt
Src Family Kinases Are Required for Integrin-mediated but Not for G Protein-coupled Receptor Stimulation of Focal Adhesion Kinase Autophosphorylation at Tyr-397
J. Biol. Chem., May 25, 2001; 276(21): 17788 - 17795.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2000 by the American Association of Cancer Research.