|
|
||||||||


* Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome "La Sapienza," Rome, Italy; and
Mediterranean Institute of Neuroscience, Neuromed, Pozzilli, Italy
Protein tyrosine kinase activation is an important requisite for leukocyte migration. Herein we demonstrate that NK cell binding to endothelium activates proline-rich tyrosine kinase 2 (Pyk-2) and the small GTP binding protein Rac that are coupled to integrin and chemokine receptors. Chemokine-mediated, but not integrin-mediated, Pyk-2 and Rac activation was sensitive to pretreatment of NK cells with pertussis toxin, a pharmacological inhibitor of Gi protein-coupled receptors. Both Pyk-2 and Rac are functionally involved in chemokine-induced NK cell migration through endothelium or ICAM-1 or VCAM-1 adhesive proteins, as shown by the use of recombinant vaccinia viruses encoding dominant negative mutants of Pyk-2 and Rac. Moreover, we found that Pyk-2 is associated with the Rac guanine nucleotide exchange factor Vav, which undergoes tyrosine phosphorylation upon integrin triggering. Finally, we provide direct evidence for the involvement of Pyk-2 in the control of both chemokine- and integrin-mediated Rac activation. Collectively, our results indicate that Pyk-2 acts as a receptor-proximal link between integrin and chemokine receptor signaling, and the Pyk-2/Rac pathway plays a pivotal role in the control of NK cell transendothelial migration.
This article has been cited by other articles:
![]() |
D. R. Spurrell, N. A. Luckashenak, D. C. Minney, A. Chaplin, J. M. Penninger, R. S. Liwski, J. L. Clements, and K. A. West Vav1 Regulates the Migration and Adhesion of Dendritic Cells J. Immunol., July 1, 2009; 183(1): 310 - 318. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Zhu, E. Boetticher, L. Wang, Y. Duan, J. Learoyd, and A. R. Leff Proline-Rich Tyrosine Kinase 2 Regulates Spreading and Migration of Eosinophils after {beta}2-Integrin Adhesion Am. J. Respir. Cell Mol. Biol., September 1, 2008; 39(3): 263 - 269. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Carlino, H. Stabile, S. Morrone, R. Bulla, A. Soriani, C. Agostinis, F. Bossi, C. Mocci, F. Sarazani, F. Tedesco, et al. Recruitment of circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy Blood, March 15, 2008; 111(6): 3108 - 3115. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Hsia, S.-T. Lim, J. A. Bernard-Trifilo, S. K. Mitra, S. Tanaka, J. den Hertog, D. N. Streblow, D. Ilic, M. H. Ginsberg, and D. D. Schlaepfer Integrin {alpha}4{beta}1 Promotes Focal Adhesion Kinase-Independent Cell Motility via {alpha}4 Cytoplasmic Domain-Specific Activation of c-Src Mol. Cell. Biol., November 1, 2005; 25(21): 9700 - 9712. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Maghazachi Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells Pharmacol. Rev., September 1, 2005; 57(3): 339 - 357. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Melnychuk, P. Smith, C. N. Kreklywich, F. Ruchti, J. Vomaske, L. Hall, L. Loh, J. A. Nelson, S. L. Orloff, and D. N. Streblow Mouse Cytomegalovirus M33 Is Necessary and Sufficient in Virus-Induced Vascular Smooth Muscle Cell Migration J. Virol., August 15, 2005; 79(16): 10788 - 10795. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Zhao and G. M. Bokoch Critical Role of Proline-Rich Tyrosine Kinase 2 in Reversion of the Adhesion-Mediated Suppression of Reactive Oxygen Species Generation by Human Neutrophils J. Immunol., June 15, 2005; 174(12): 8049 - 8055. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Riol-Blanco, N. Sanchez-Sanchez, A. Torres, A. Tejedor, S. Narumiya, A. L. Corbi, P. Sanchez-Mateos, and J. L. Rodriguez-Fernandez The Chemokine Receptor CCR7 Activates in Dendritic Cells Two Signaling Modules That Independently Regulate Chemotaxis and Migratory Speed J. Immunol., April 1, 2005; 174(7): 4070 - 4080. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-C. Aasheim, J. Delabie, and E. F. Finne Ephrin-A1 binding to CD4+ T lymphocytes stimulates migration and induces tyrosine phosphorylation of PYK2 Blood, April 1, 2005; 105(7): 2869 - 2876. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. F. Barber, M. Faure, and E. O. Long LFA-1 Contributes an Early Signal for NK Cell Cytotoxicity J. Immunol., September 15, 2004; 173(6): 3653 - 3659. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Rouhiainen, J. Kuja-Panula, E. Wilkman, J. Pakkanen, J. Stenfors, R. K. Tuominen, M. Lepantalo, O. Carpen, J. Parkkinen, and H. Rauvala Regulation of monocyte migration by amphoterin (HMGB1) Blood, August 15, 2004; 104(4): 1174 - 1182. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Gismondi, L. Cifaldi, C. Mazza, S. Giliani, S. Parolini, S. Morrone, J. Jacobelli, E. Bandiera, L. Notarangelo, and A. Santoni Impaired natural and CD16-mediated NK cell cytotoxicity in patients with WAS and XLT: ability of IL-2 to correct NK cell functional defect Blood, July 15, 2004; 104(2): 436 - 443. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Pontow, N. V. Heyden, S. Wei, and L. Ratner Actin Cytoskeletal Reorganizations and Coreceptor-Mediated Activation of Rac during Human Immunodeficiency Virus-Induced Cell Fusion J. Virol., July 1, 2004; 78(13): 7138 - 7147. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-S. Shi and J. H. Kehrl Pyk2 Amplifies Epidermal Growth Factor and c-Src-induced Stat3 Activation J. Biol. Chem., April 23, 2004; 279(17): 17224 - 17231. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. McLeod, A. J. Shum, R. L. Lee, F. Takei, and M. R. Gold The Rap GTPases Regulate Integrin-mediated Adhesion, Cell Spreading, Actin Polymerization, and Pyk2 Tyrosine Phosphorylation in B Lymphocytes J. Biol. Chem., March 26, 2004; 279(13): 12009 - 12019. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. K. Chandhoke, M. Williams, E. Schaefer, L. Zorn, and S. D. Blystone {beta}3 integrin phosphorylation is essential for Arp3 organization into leukocyte {alpha}V{beta}3-vitronectin adhesion contacts J. Cell Sci., March 15, 2004; 117(8): 1431 - 1441. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |