![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 12, Issue 7, 1937-1956, July 2001
Department of Biochemistry and Molecular Biology,
University of Massachusetts, Amherst, Massachusetts 01003
Adhesion of cells to an extracellular matrix is
characterized by several discrete morphological and functional stages
beginning with cell-substrate attachment, followed by cell spreading,
migration, and immobilization. We find that although arachidonic acid
release is rate-limiting in the overall process of adhesion, its
oxidation by lipoxygenase and cyclooxygenases regulates, respectively,
the cell spreading and cell migration stages. During the adhesion of
NIH-3T3 cells to fibronectin, two functionally and kinetically distinct
phases of arachidonic acid release take place. An initial transient
arachidonate release occurs during cell attachment to fibronectin, and
is sufficient to signal the cell spreading stage after its oxidation by
5-lipoxygenase to leukotrienes. A later sustained arachidonate release
occurs during and after spreading, and signals the subsequent migration
stage through its oxidation to prostaglandins by newly synthesized
cyclooxygenase-2. In signaling migration, constitutively expressed
cyclooxygenase-1 appears to contribute ~25% of prostaglandins
synthesized compared with the inducible cyclooxygenase-2. Both the
second sustained arachidonate release, and cyclooxygenase-2 protein
induction and synthesis, appear to be regulated by the
mitogen-activated protein kinase extracellular signal-regulated
kinase (ERK)1/2. The initial cell attachment-induced transient
arachidonic acid release that signals spreading through lipoxygenase
oxidation is not sensitive to ERK1/2 inhibition by PD98059, whereas
PD98059 produces both a reduction in the larger second arachidonate
release and a blockade of induced cyclooxygenase-2 protein expression
with concomitant reduction of prostaglandin synthesis. The second
arachidonate release, and cyclooxygenase-2 expression and activity,
both appear to be required for cell migration but not for the preceding
stages of attachment and spreading. These data suggest a bifurcation in
the arachidonic acid adhesion-signaling pathway, wherein lipoxygenase
oxidation generates leukotriene metabolites regulating the spreading
stage of cell adhesion, whereas ERK 1/2-induced cyclooxygenase
synthesis results in oxidation of a later release, generating
prostaglandin metabolites regulating the later migration stage.
This article has been cited by other articles:
|
|
 |
|
  K. V. Vijayan and P. F. Bray Molecular Mechanisms of Prothrombotic Risk Due to Genetic Variations in Platelet Genes: Enhanced Outside-In Signaling Through the Pro33 Variant of Integrin {beta}3. Experimental Biology and Medicine, May 1, 2006; 231(5): 505 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Dronadula, Z. Liu, C. Wang, H. Cao, and G. N. Rao STAT-3-dependent Cytosolic Phospholipase A2 Expression Is Required for Thrombin-induced Vascular Smooth Muscle Cell Motility J. Biol. Chem., January 28, 2005; 280(4): 3112 - 3120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Neeli, Z. Liu, N. Dronadula, Z. A. Ma, and G. N. Rao An Essential Role of the Jak-2/STAT-3/Cytosolic Phospholipase A2 Axis in Platelet-derived Growth Factor BB-induced Vascular Smooth Muscle Cell Motility J. Biol. Chem., October 29, 2004; 279(44): 46122 - 46128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mehrabian and H. Allayee Vascular Cross-Talk: A Conversation Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1748 - 1749. [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Cai, L. Lanting, and R. Natarajan Growth factors induce monocyte binding to vascular smooth muscle cells: implications for monocyte retention in atherosclerosis Am J Physiol Cell Physiol, September 1, 2004; 287(3): C707 - C714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Green, R. A. Stockton, C. Johnson, and B. S. Jacobson 5-Lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers Am J Physiol Cell Physiol, August 1, 2004; 287(2): C373 - C383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Finkelstein, W. Chang, P.-H. G. Chao, D. Gruber, A. Minden, C. T. Hung, and J. C. Bulinski Roles of microtubules, cell polarity and adhesion in electric-field-mediated motility of 3T3 fibroblasts J. Cell Sci., March 15, 2004; 117(8): 1533 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Chuang, C. Helvig, M. Taimi, H. A. Ramshaw, A. H. Collop, M.'a. Amad, J. A. White, M. Petkovich, G. Jones, and B. Korczak CYP2U1, a Novel Human Thymus- and Brain-specific Cytochrome P450, Catalyzes {omega}- and ({omega}-1)-Hydroxylation of Fatty Acids J. Biol. Chem., February 20, 2004; 279(8): 6305 - 6314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chen, N. Li, S. Wang, N. Wu, J. Hong, X. Jiao, M. J. Krasna, D. G. Beer, and C. S. Yang Leukotriene A4 Hydrolase in Rat and Human Esophageal Adenocarcinomas and Inhibitory Effects of Bestatin J Natl Cancer Inst, July 16, 2003; 95(14): 1053 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V. Vijayan, Y. Liu, J.-F. Dong, and P. F. Bray Enhanced Activation of Mitogen-activated Protein Kinase and Myosin Light Chain Kinase by the Pro33 Polymorphism of Integrin beta 3 J. Biol. Chem., January 31, 2003; 278(6): 3860 - 3867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sajid, K. V. Vijayan, S. Souza, and P. F. Bray PlA Polymorphism of Integrin {beta}3 Differentially Modulates Cellular Migration on Extracellular Matrix Proteins Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 1984 - 1989. [Abstract] [Full Text] [PDF]
|
|
