title: Focal adhesion kinase regulation of neovascularization.
abstract: In this review, we discuss the role of focal adhesion kinase (FAK), an intracellular tyrosine kinase, in endothelial cells in relation to neovascularization. Genetic and in vitro studies have identified critical factors, receptor systems, and their intracellular signaling components that regulate the neovasculogenic phenotypes of endothelial cells. Among these factors, FAK appears to regulate several aspects of endothelial cellular behavior, including migration, survival, cytoskeletal organization, as well as cell proliferation. Upon adhesion of endothelial cells to extracellular matrix (ECM) ligands, integrins cluster on the plane of plasma-membrane, while cytoplasmic domains of integrins interact with cytoskeletal proteins and signaling molecules including FAK. However, FAK not only serves as a critical component of integrin signaling, but is also a downstream element of the VEGF/VEGF-receptor and other ligand-receptor systems that regulate neovascularization. A complete understanding of FAK-mediated neovascularization, therefore, should address the molecular and cellular mechanisms that regulate the biology of FAK. Continued research on FAK may, therefore, yield novel therapies to improve treatment modalities for the pathological neovascularization associated with diseases.
authors: Department of Pharmacology, University of Illinois, 835 S. Wolcott, Room E403, Mail code 868, Chicago, IL 60612, USA. kkwary@uic.edu
authors: Kishore K
authors: KK
authors: Wary
authors: Erin E
authors: EE
authors: Kohler
authors: Ishita
authors: I
authors: Chatterjee
references: Mol Cell Biol. 1994 Mar;14(3):1680-8
references: 7509446
references: Mol Cell Biol. 2001 Mar;21(5):1565-72
references: 11238893
references: Microvasc Res. 1977 Jul;14(1):53-65
references: 895546
references: Blood. 2009 Jan 15;113(3):563-6
references: 18957687
references: IUBMB Life. 2007 Nov;59(11):709-16
references: 17968709
references: Dev Dyn. 2007 Aug;236(8):2089-100
references: 17654716
references: J Cell Biol. 1998 Oct 19;143(2):547-60
references: 9786962
references: Cell. 2000 Jan 7;100(1):57-70
references: 10647931
references: EMBO Mol Med. 2010 Dec;2(12):516-28
references: 21154724
references: Nat Cell Biol. 2010 Oct;12(10):943-53
references: 20871601
references: Blood. 1995 Jul 1;86(1):156-63
references: 7795222
references: Nature. 2002 Jun 27;417(6892):954-8
references: 12087404
references: Int J Dev Biol. 2010;54(6-7):1151-63
references: 20711992
references: Nature. 1994 Dec 22-29;372(6508):786-91
references: 7997267
references: Cancer Metastasis Rev. 2009 Jun;28(1-2):35-49
references: 19169797
references: Nature. 2006 Jul 27;442(7101):453-6
references: 16799567
references: J Cell Biol. 1993 Nov;123(4):993-1005
references: 8227154
references: Biochim Biophys Acta. 2001 Aug 22;1540(2):147-53
references: 11513976
references: Nature. 1995 Oct 12;377(6549):539-44
references: 7566154
references: Microvasc Res. 2007 Sep-Nov;74(2-3):159-71
references: 17950369
references: Biochim Biophys Acta. 2001 Jul 25;1540(1):1-21
references: 11476890
references: J Cell Biol. 2005 Jun 20;169(6):941-52
references: 15967814
references: EMBO J. 1998 Aug 3;17(15):4346-57
references: 9687503
references: Cell. 1996 Aug 9;86(3):353-64
references: 8756718
references: Nat Rev Cancer. 2002 Jul;2(7):489-501
references: 12094235
references: J Cell Biol. 2006 Jan 2;172(1):151-62
references: 16391003
references: J Biol Chem. 1996 Feb 16;271(7):3877-83
references: 8632007
references: Nature. 2009 Feb 12;457(7231):887-91
references: 19129762
references: Nature. 2007 Feb 15;445(7129):781-4
references: 17259972
references: Cell. 2003 Jan 10;112(1):19-28
references: 12526790
references: Nature. 2005 Dec 15;438(7070):937-45
references: 16355211
references: Clin Cancer Res. 2003 Jun;9(6):2157-65
references: 12796381
references: Circ Res. 2003 Feb 21;92(3):300-7
references: 12595342
references: Dev Dyn. 2010 Oct;239(10):2570-83
references: 20737513
references: Physiology (Bethesda). 2005 Jun;20:180-93
references: 15888575
references: Biochim Biophys Acta. 2004 May 25;1678(2-3):111-25
references: 15157737
references: Microvasc Res. 2007 Sep-Nov;74(2-3):121-30
references: 17574280
references: Dev Cell. 2009 Feb;16(2):222-31
references: 19217424
references: Microvasc Res. 2007 Sep-Nov;74(2-3):72-84
references: 17560615
references: Microvasc Res. 2003 Sep;66(2):102-12
references: 12935768
references: Front Biosci. 2004 May 01;9:1254-66
references: 14977542
references: Cell. 1998 Sep 4;94(5):625-34
references: 9741627
references: J Angiogenes Res. 2009 Nov 16;1:8
references: 20016694
references: Bioessays. 1998 Aug;20(8):611-4
references: 9780835
references: Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192-6
references: 1594631
references: Curr Opin Mol Ther. 2004 Feb;6(1):54-70
references: 15011782
references: Genes Dev. 2000 May 1;14(9):1132-45
references: 10809671
references: Development. 2004 Jun;131(11):2749-62
references: 15148304
references: Cancer Res. 2000 Jan 15;60(2):203-12
references: 10667560
references: Curr Top Dev Biol. 2006;76:217-57
references: 17118268
references: Cell. 2009 Jun 12;137(6):1124-35
references: 19524514
references: Mol Cell Biol. 1997 Mar;17(3):1702-13
references: 9032297
references: Biochem Biophys Res Commun. 1995 Apr 6;209(1):300-9
references: 7726850
references: Curr Opin Cell Biol. 2010 Oct;22(5):617-25
references: 20817428
references: Nature. 1997 Apr 17;386(6626):671-4
references: 9109485
references: Dev Cell. 2009 Jan;16(1):70-82
references: 19154719
references: J Cell Sci. 2003 Apr 15;116(Pt 8):1409-16
references: 12640026
references: Gene Expr Patterns. 2007 Feb;7(4):461-70
references: 17161657
references: Cell. 1997 Jun 13;89(6):981-90
references: 9200616
references: Front Biosci. 1999 Jan 15;4:D102-13
references: 9889179
references: Pharmacol Rep. 2008 Jan-Feb;60(1):139-43
references: 18276995
references: Mol Cell Biol. 1993 Feb;13(2):785-91
references: 8423801
references: Nature. 2007 Feb 15;445(7129):776-80
references: 17259973
references: Curr Opin Genet Dev. 2003 Aug;13(4):408-12
references: 12888015
references: Oncogene. 2006 Sep 28;25(44):5969-84
references: 16682956
references: Cell. 1996 Nov 15;87(4):733-43
references: 8929541
references: Nat Rev Mol Cell Biol. 2007 Jun;8(6):464-78
references: 17522591
references: Nat Rev Cancer. 2003 Jun;3(6):422-33
references: 12778132
references: Cell. 1997 Dec 26;91(7):949-60
references: 9428518
references: Nat Med. 2003 Jun;9(6):653-60
references: 12778163