Components of Focal adhesion complex


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Common Components of Focal Adhesions

For information on interactions between components, visit Adhesome FA Network [1] .

Table: Components of focal adhesion complex and their proposed function.

Component

Function


Receptor/matrix binding

Integrins

Transmembrane receptors that bind to ECM through their extracellular domains and to cellular adaptor proteins through their cytoplasmic domain. Mediate formation and maturation of focal adhesions by sensing the environment.

[2, 3, 4]

Syndecan-4

Cell surface heparin-sulfate proteoglycan that acts as a co-receptor and mediates signals along with integrins for focal adhesion assembly

[5]

Layilin

Transmembrane hyaluronic acid receptor localized at the peripheral ruffles of migrating cells. Binds to the FERM domain of talin and docks it to membrane. Mediates formation of transient adhesions, but not present in stable adhesions.

[6, 7]

uPAR (Urokinase plasminogen activator receptor)

GPI-linked receptor that forms complexes with Integrins and regulates its ligand specificity and adhesion formation.

[8, 9, 10, 11]

Fibronectin

Extracellular ligand that bind to cell surface receptors and initiate formation of nascent focal adhesions


Vitronectin

Glycoprotein found in plasma and ECM. Binds to cell surface receptors such as uPAR and integrins to mediate cell adhesions.

[9]

Collagen

Extracellular matrix protein that binds to receptors of integrin, receptor tyrosine kinase and Ig-like superfamilies and thereby mediate cell adhesion.

[12]

Caveolin

Membrane protein that forms complexes with integrin and uPAR and regulates ligand-induced signaling by binding signaling molecules such as Src kinase.

[8]

Dystroglycan

Cell adhesion molecule that indirectly interacts with vinculin through vinexin and modulates focal adhesions maturation and turnover rates.

[13]

Linkage to actin cytoskeleton and force transduction

Talin

Binds to cytoplasmic tails of integrins and activates them and links the integrins to actin cytoskeleton through its actin-binding domains

[14]

Kindlins

Adaptor protein that links integrins to F-actin; act synergistically with talin to activate integrins

[15]

Vinculin

Adaptor protein that links talin to F-actin, regulates paxillin recruitment


[16, 17]

α-actinin

Actin crosslinking protein that links integrin signaling to the actin cytoskeleton; critical for adhesion elongation and reinforcement

[18, 19]

Filamin

Actin crosslinking protein that links integrin signaling to the actin cytoskeleton


[20, 21]

Paxillin

Scaffolding protein that gets recruited to early adhesions and can bind signaling molecules (e.g. kinases, phosphatases, Rho family of GTPases), adhesion molecules (e.g. α-integrin) and actin-binding proteins (e.g. vinculin and parvin). It gets phosphorylated by Src-FAK; its Ser phosphorylation regulates adhesion turnover.

[22, 23, 24]

p130CAS

Signaling and scaffold protein that leads to Rho GTPase activation; gets phosphorylated by Src-FAK

[25, 26]

CRK

Adaptor protein with SH2 domain; gets recruited after tyrosine phosphorylation of p130CAS

[27, 28]

Tensin

Adaptor protein that links the integrin signaling to the actin cytoskeleton at later stages of focal adhesions and fibrillar adhesions


[29, 30]

Zyxin

Adaptor/scaffolding protein that links integrin signaling to the actin cytoskeleton at later stages of focal adhesions


[31, 32]

Parvin/ actopaxin

Forms complexes with PINCH and ILK at integrin adhesion sites and controls Rac activity and eventually actin polymerization. Parvin B promotes Rac activity, whereas Parvin A inhibits Rac activity.

[33]

PINCH

Forms complexes with ILK and parvin at integrin attachment sites and transduces integrin-mediated signaling.

[34]

Phosphatidylinositol 4,5-bisphosphate (PIP2)

Lipid molecule that binds and activates cytoskeletal structural proteins (e.g. talin and vinculin). Hence it regulates their localization to focal adhesion, actin polymerization and adhesion disassembly.

[35]

Ponsin

Adaptor protein that binds to vinculin and mediates cell adhesion by regulating signal transduction and cytoskeletal organization

[36]

Vinexin

Adaptor protein that binds to vinculin and mediates cell adhesion by regulating signal transduction and cytoskeletal organization

[36]

Palladin

Regulates cytoskeletal reorganization by directly binding to F-actin and crosslinking them as well as by serving as a molecular scaffold for other structural and signaling proteins within the cell adhesions.

[37]

GRB7

Adaptor molecule linking signals initiated upon receptor-matrix binding to downstream signaling pathways.

[38]

Intracellular signal transduction

Focal adhesion kinase (FAK)

Non-receptor tyrosine kinase that acts as a signaling component in focal adhesions and controls their turnover in complex with Src.

[39]

c-Src

Signaling component (tyrosine kinase) that modifies FAK, paxillin and p130Cas; belongs to Src family of kinases (SFKs)

[40]

Fyn

Signaling component that strengthens adhesions; belongs to Src family of kinases (SFKs)

[41]

Receptor-like protein tyrosine phosphatase (RPTPα)

Signaling component that activates Fyn

[42, 43]

Integrin linker kinase (ILK)

Signaling component (serine/threonine kinase) and scaffolding protein that interacts with parvin, kindlin, integrins


[34, 44]

Protein Kinase C (PKC)

Recruited to focal adhesions through a direct interaction with Syndecan-4, where they may function in phosphorylating other cytoskeletal or signaling proteins.

[45]

Phosphotidylinositol 3-kinase (PI3K)

Signaling component (lipid kinase) that influences Rho GTPases and other signaling components

[46, 47]

Myosin light chain kinase (MLCK)

Serine/threonine kinase that phosphorylates the regulatory myosin light chains of myosin II, in order to facilitate myosin binding to actin. It therefore aids contractility and focal adhesion disassembly.

[48]

Rho kinase (ROCK)

Effector of RhoA that gets activated by binding to RhoA. It mediates myosin-based contractions and hence formation of stress fibres, trailing edge retraction and maturation of focal adhesions.

[49, 50]

Abl and related (Arg) kinases

Nonreceptor tyrosine kinase localized at focal adhesions that regulates actin cytoskeleton by directly binding to F-actin. They decrease cell migration by preventing formation of Crk-CAS complexes and inhibiting myosin contractility.

[51, 52]

LAR

Transmembrane protein tyrosine phosphatase that regulates focal adhesion disassembly


[53]

SHPS-1

Tyrosine phosphorylated transmembrane protein that recruits SHP-2 (phosphatase) upon integrin-mediated cell adhesion and thereby facilitates cytoskeletal reorganization and cell migration through the phosphatase.

[54]

DRAL

Adaptor protein that binds to integrin and regulates integrin function and signaling.

[55]

14-3-3-beta

Regulates integrin-mediated cell adhesion and spreading by binding to integrins and various signaling molecules simultaneously.

[56, 57]

p21-activated kinase (PAK)

Signaling component that is induced by Rac and CDC42 and localizes to foal adhesions functioning in focal adhesion disassembly.

[58]

SHP-2

Tyrosine phosphatase that mediates cytoskeletal reorganization and cell migration by binding to SHPS-1.

[54]

SHIP-2

Inositol phosphatase that binds to the adaptor protein p130cas and promotes cell adhesion and spreading.

[59]

Rac1

Ras-related small GTPase that gets activated by integrin signaling at the leading edge of migrating cells; aids nascent adhesion formation and protrusion of lamellipodia.

[60, 61]

RhoA

Ras-related small GTPase that gets activated by integrin signaling at late stages of cell spreading and promotes actomyosin contractility. This aids adhesion growth/maturation and retraction of the trailing edge.

[61, 62]

RhoG

Guanine nucleotide exchange factor ( GEF) that activates Rac1 by binding to ELMO.

[63]

Paxillin kinase linker

Phosphorylated by FAK and Src upon cell adhesion and localized to focal adhesions by binding to paxillin, this GAP regulates directional cell spreading by modulating Rac and Cdc42 activities.

[64]

DOCK-180 (180KDa protein downstream of CRK) Guanine exchange factor for Rac and regulates cell migration by binding to focal adhesion proteins such as Crk, ELMO and ANKRD28.
[40, 65]

Ankyrin repeat domain 28 (ANKRD28)

Binds to DOCK-180

[66]

PIX proteins (PAK interacting exchange factors)

Guanine nucleotide exchange factor that regulates focal adhesion assembly as well as disassembly by involving in processes such as cytoskeletal rearrangements and focal adhesion components turnover.

[67, 68]

GIT (G protein-coupled receptor (GPCR) kinase-interacting protein)

A ADP-ribosylation factor GAP that binds to paxillin, PIX and FAK; activates Rac1/Cdc42.

[67]

p190RhoGEF

RhoGEF required for localized Rho activation to promote myosin contractility and aid adhesion maturation

[69]

LARG

RhoGEF that gets recruited at adhesion site in a tension- dependent manner, activated by Fyn, a Src-family kinase. It activates Rho to aid adhesion maturation.

[70]

GEF-H1

RhoGEF that gets recruited at adhesion site in a tension- dependent manner, activates Rho to aid adhesion maturation; Enhanced by FAK-Ras-ERK signaling.

[70]

PDZRhoGEF

RhoGEF required for localized Rho activation to promote trailing edge retraction via ROCK pathway.

[50]

Asef

GEF for Rac1 at the leading edge; aids nascent adhesion formation

[71]

GRAF (GTPase regulator associated with focal adhesions)

Regulates integrin-mediated signaling by binding to FAK and promoting the GTPase activity of RhoA and CDC42.

[72]

ASAP1 (ARF GTPase-activating protein 1)

ADP-ribosylation- factor [ARF] GAP that binds to FAK, gets phosphorylated by Src and influences paxillin binding, hence focal adhesion assembly.

[73]

ARHGAP22

RhoGAP that converts Rac1 to inactive state in a tension-dependent manner; suppresses protrusion and aid focal adhesion maturation.

[74, 75]

p190RhoGAP

Gets phosphorylated by FAK, localizes to membrane via syndecan signaling; prevents RhoA activation during membrane protrusion.

[76, 77]

p120RasGAP

Adapter that binds to FAK and aids phosphorylation of p190RhoGAP; thus prevents RhoA activation during membrane protrusion.

[77]

cdGAP

RhoGAP that converts Rac1 and cdc42 to inactive state; suppresses protrusion and aid focal adhesion maturation.

[78]

Calpain II

Calcium-dependent cysteine protease that can cleave focal adhesion proteins such as talin, FAK and paxillin, thus regulating adhesion turnover and thereby cell migration.

[79]

Syntenin

PDZ domain-containing scaffolding protein that binds to syndecans, PIP2, FAK and Src. It activates Src and its downstream signaling thus promoting cell motility.

[80, 81]

Syndesmos

Adaptor protein at the focal adhesion sites that binds to the cytoplasmic region of syndecans and promotes cell spreading and actin reorganization.

[82]

Csk

Functions in insulin-stimulated dephosphorylation of FAK and paxillin, thereby regulating cytoskeletal reorganization and cell migration.

[83]

Actin polymerization and regulation

Ena/Vasp

Regulates actin filament assembly by recruiting profilin bound to actin monomers. Also binds to vinculin and zyxin and thus links the actin cytoskeleton to the focal adhesion components.

[84]

ERM proteins

Regulates actin filament assembly ny directly binding to N-WASP. Act as membrane-cytoskeleton linker and thus regulates the organization and maintenance of specialized membrane domains.

[85, 86]

Nexillin

F-actin binding protein and also has actin-crosslinking functions.

[87]

Cysteine-rich protein (CRP)

LIM domain-containing proteins that directly binds to actin and bundles the filaments and also stabilizes alpha-actinin interactions with F-actin.

[88]

References

  1. Zaidel-Bar R., Itzkovitz S., Ma’ayan A., Iyengar R. & Geiger B. Functional atlas of the integrin adhesome. Nat. Cell Biol. 2007; 9(8):858-67. [PMID: 17671451]
  2. Takada Y., Ye X. & Simon S. The integrins. Genome Biol. 2007; 8(5):215. [PMID: 17543136]
  3. Geiger B., Spatz JP. & Bershadsky AD. Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell Biol. 2009; 10(1):21-33. [PMID: 19197329]
  4. Barczyk M., Carracedo S. & Gullberg D. Integrins. Cell Tissue Res. 2010; 339(1):269-80. [PMID: 19693543]
  5. Woods A. & Couchman JR. Syndecan-4 and focal adhesion function. Curr. Opin. Cell Biol. 2001; 13(5):578-83. [PMID: 11544026]
  6. Bono P., Rubin K., Higgins JM. & Hynes RO. Layilin, a novel integral membrane protein, is a hyaluronan receptor. Mol. Biol. Cell 2001; 12(4):891-900. [PMID: 11294894]
  7. Wegener KL., Basran J., Bagshaw CR., Campbell ID., Roberts GC., Critchley DR. & Barsukov IL. Structural basis for the interaction between the cytoplasmic domain of the hyaluronate receptor layilin and the talin F3 subdomain. J. Mol. Biol. 2008; 382(1):112-26. [PMID: 18638481]
  8. Wei Y., Yang X., Liu Q., Wilkins JA. & Chapman HA. A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signaling. J. Cell Biol. 1999; 144(6):1285-94. [PMID: 10087270]
  9. Madsen CD. & Sidenius N. The interaction between urokinase receptor and vitronectin in cell adhesion and signalling. Eur. J. Cell Biol. 2008; 87(8-9):617-29. [PMID: 18353489]
  10. Abu-Ali S., Sugiura T., Takahashi M., Shiratsuchi T., Ikari T., Seki K., Hiraki A., Matsuki R. & Shirasuna K. Expression of the urokinase receptor regulates focal adhesion assembly and cell migration in adenoid cystic carcinoma cells. J. Cell. Physiol. 2005; 203(2):410-9. [PMID: 15521066]
  11. Salasznyk RM., Zappala M., Zheng M., Yu L., Wilkins-Port C. & McKeown-Longo PJ. The uPA receptor and the somatomedin B region of vitronectin direct the localization of uPA to focal adhesions in microvessel endothelial cells. Matrix Biol. 2007; 26(5):359-70. [PMID: 17344041]
  12. Heino J. The collagen family members as cell adhesion proteins. Bioessays 2007; 29(10):1001-10. [PMID: 17876790]
  13. Thompson O., Moore CJ., Hussain SA., Kleino I., Peckham M., Hohenester E., Ayscough KR., Saksela K. & Winder SJ. Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan. J. Cell. Sci. 2010; 123(Pt 1):118-27. [PMID: 20016072]
  14. Critchley DR. & Gingras AR. Talin at a glance. J. Cell. Sci. 2008; 121(Pt 9):1345-7. [PMID: 18434644]
  15. Karaköse E., Schiller HB. & Fässler R. The kindlins at a glance. J. Cell. Sci. 2010; 123(Pt 14):2353-6. [PMID: 20592181]
  16. Ziegler WH., Liddington RC. & Critchley DR. The structure and regulation of vinculin. Trends Cell Biol. 2006; 16(9):453-60. [PMID: 16893648]
  17. Humphries JD., Wang P., Streuli C., Geiger B., Humphries MJ. & Ballestrem C. Vinculin controls focal adhesion formation by direct interactions with talin and actin. J. Cell Biol. 2007; 179(5):1043-57. [PMID: 18056416]
  18. Sjöblom B., Salmazo A. & Djinović-Carugo K. Alpha-actinin structure and regulation. Cell. Mol. Life Sci. 2008; 65(17):2688-701. [PMID: 18488141]
  19. Choi CK., Vicente-Manzanares M., Zareno J., Whitmore LA., Mogilner A. & Horwitz AR. Actin and alpha-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat. Cell Biol. 2008; 10(9):1039-50. [PMID: 19160484]
  20. Feng Y. & Walsh CA. The many faces of filamin: a versatile molecular scaffold for cell motility and signalling. Nat. Cell Biol. 2004; 6(11):1034-8. [PMID: 15516996]
  21. Kim H., Sengupta A., Glogauer M. & McCulloch CA. Filamin A regulates cell spreading and survival via beta1 integrins. Exp. Cell Res. 2008; 314(4):834-46. [PMID: 18177638]
  22. Nikolopoulos SN. & Turner CE. Actopaxin, a new focal adhesion protein that binds paxillin LD motifs and actin and regulates cell adhesion. J. Cell Biol. 2000; 151(7):1435-48. [PMID: 11134073]
  23. Mofrad MR., Golji J., Abdul Rahim NA. & Kamm RD. Force-induced unfolding of the focal adhesion targeting domain and the influence of paxillin binding. Mech Chem Biosyst 2004; 1(4):253-65. [PMID: 16783922]
  24. Deakin NO. & Turner CE. Paxillin comes of age. J. Cell. Sci. 2008; 121(Pt 15):2435-44. [PMID: 18650496]
  25. Defilippi P., Di Stefano P. & Cabodi S. p130Cas: a versatile scaffold in signaling networks. Trends Cell Biol. 2006; 16(5):257-63. [PMID: 16581250]
  26. Geiger B. A role for p130Cas in mechanotransduction. Cell 2006; 127(5):879-81. [PMID: 17129774]
  27. Kiyokawa E., Hashimoto Y., Kobayashi S., Sugimura H., Kurata T. & Matsuda M. Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Genes Dev. 1998; 12(21):3331-6. [PMID: 9808620]
  28. Chodniewicz D. & Klemke RL. Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold. Biochim. Biophys. Acta 2004; 1692(2-3):63-76. [PMID: 15246680]
  29. Lo SH. Tensin. Int. J. Biochem. Cell Biol. 2004; 36(1):31-4. [PMID: 14592531]
  30. Chen H. & Lo SH. Regulation of tensin-promoted cell migration by its focal adhesion binding and Src homology domain 2. Biochem. J. 2003; 370(Pt 3):1039-45. [PMID: 12495434]
  31. Hoffman LM., Jensen CC., Kloeker S., Wang CL., Yoshigi M. & Beckerle MC. Genetic ablation of zyxin causes Mena/VASP mislocalization, increased motility, and deficits in actin remodeling. J. Cell Biol. 2006; 172(5):771-82. [PMID: 16505170]
  32. Colombelli J., Besser A., Kress H., Reynaud EG., Girard P., Caussinus E., Haselmann U., Small JV., Schwarz US. & Stelzer EH. Mechanosensing in actin stress fibers revealed by a close correlation between force and protein localization. J. Cell. Sci. 2009; 122(Pt 10):1665-79. [PMID: 19401336]
  33. Sepulveda JL. & Wu C. The parvins. Cell. Mol. Life Sci. 2006; 63(1):25-35. [PMID: 16314921]
  34. Legate KR., Montañez E., Kudlacek O. & Fässler R. ILK, PINCH and parvin: the tIPP of integrin signalling. Nat. Rev. Mol. Cell Biol. 2006; 7(1):20-31. [PMID: 16493410]
  35. Raucher D., Stauffer T., Chen W., Shen K., Guo S., York JD., Sheetz MP. & Meyer T. Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion. Cell 2000; 100(2):221-8. [PMID: 10660045]
  36. Kioka N., Ueda K. & Amachi T. Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction. Cell Struct. Funct. 2002; 27(1):1-7. [PMID: 11937713]
  37. Goicoechea SM., Arneman D. & Otey CA. The role of palladin in actin organization and cell motility. Eur. J. Cell Biol. 2008; 87(8-9):517-25. [PMID: 18342394]
  38. Shen TL. & Guan JL. Grb7 in intracellular signaling and its role in cell regulation. Front. Biosci. 2004; 9:192-200. [PMID: 14766359]
  39. Schaller MD. Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J. Cell. Sci. 2010; 123(Pt 7):1007-13. [PMID: 20332118]
  40. Huveneers S. & Danen EH. Adhesion signaling – crosstalk between integrins, Src and Rho. J. Cell. Sci. 2009; 122(Pt 8):1059-69. [PMID: 19339545]
  41. Reddy KB., Smith DM. & Plow EF. Analysis of Fyn function in hemostasis and alphaIIbbeta3-integrin signaling. J. Cell. Sci. 2008; 121(Pt 10):1641-8. [PMID: 18430780]
  42. Jiang G., Huang AH., Cai Y., Tanase M. & Sheetz MP. Rigidity sensing at the leading edge through alphavbeta3 integrins and RPTPalpha. Biophys. J. 2006; 90(5):1804-9. [PMID: 16339875]
  43. von Wichert G., Jiang G., Kostic A., De Vos K., Sap J. & Sheetz MP. RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages. J. Cell Biol. 2003; 161(1):143-53. [PMID: 12682088]
  44. Tucker KL., Sage T., Stevens JM., Jordan PA., Jones S., Barrett NE., St-Arnaud R., Frampton J., Dedhar S. & Gibbins JM. A dual role for integrin-linked kinase in platelets: regulating integrin function and alpha-granule secretion. Blood 2008; 112(12):4523-31. [PMID: 18772455]
  45. Lim ST., Longley RL., Couchman JR. & Woods A. Direct binding of syndecan-4 cytoplasmic domain to the catalytic domain of protein kinase C alpha (PKC alpha) increases focal adhesion localization of PKC alpha. J. Biol. Chem. 2003; 278(16):13795-802. [PMID: 12571249]
  46. Merlot S. & Firtel RA. Leading the way: Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J. Cell. Sci. 2003; 116(Pt 17):3471-8. [PMID: 12893811]
  47. Kölsch V., Charest PG. & Firtel RA. The regulation of cell motility and chemotaxis by phospholipid signaling. J. Cell. Sci. 2008; 121(Pt 5):551-9. [PMID: 18287584]
  48. Webb DJ., Donais K., Whitmore LA., Thomas SM., Turner CE., Parsons JT. & Horwitz AF. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat. Cell Biol. 2004; 6(2):154-61. [PMID: 14743221]
  49. Amano M., Chihara K., Kimura K., Fukata Y., Nakamura N., Matsuura Y. & Kaibuchi K. Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science 1997; 275(5304):1308-11. [PMID: 9036856]
  50. Iwanicki MP., Vomastek T., Tilghman RW., Martin KH., Banerjee J., Wedegaertner PB. & Parsons JT. FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts. J. Cell. Sci. 2008; 121(Pt 6):895-905. [PMID: 18303050]
  51. Kain KH. & Klemke RL. Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes. J. Biol. Chem. 2001; 276(19):16185-92. [PMID: 11279004]
  52. Peacock JG., Miller AL., Bradley WD., Rodriguez OC., Webb DJ. & Koleske AJ. The Abl-related gene tyrosine kinase acts through p190RhoGAP to inhibit actomyosin contractility and regulate focal adhesion dynamics upon adhesion to fibronectin. Mol. Biol. Cell 2007; 18(10):3860-72. [PMID: 17652459]
  53. Serra-Pagès C., Kedersha NL., Fazikas L., Medley Q., Debant A. & Streuli M. The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions. EMBO J. 1995; 14(12):2827-38. [PMID: 7796809]
  54. Inagaki K., Yamao T., Noguchi T., Matozaki T., Fukunaga K., Takada T., Hosooka T., Akira S. & Kasuga M. SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility. EMBO J. 2000; 19(24):6721-31. [PMID: 11118207]
  55. Wixler V., Geerts D., Laplantine E., Westhoff D., Smyth N., Aumailley M., Sonnenberg A. & Paulsson M. The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes. J. Biol. Chem. 2000; 275(43):33669-78. [PMID: 10906324]
  56. Han DC., Rodriguez LG. & Guan JL. Identification of a novel interaction between integrin beta1 and 14-3-3beta. Oncogene 2001; 20(3):346-57. [PMID: 11313964]
  57. Deakin NO., Bass MD., Warwood S., Schoelermann J., Mostafavi-Pour Z., Knight D., Ballestrem C. & Humphries MJ. An integrin-alpha4-14-3-3zeta-paxillin ternary complex mediates localised Cdc42 activity and accelerates cell migration. J. Cell. Sci. 2009; 122(Pt 10):1654-64. [PMID: 19401330]
  58. Manser E., Huang HY., Loo TH., Chen XQ., Dong JM., Leung T. & Lim L. Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes. Mol. Cell. Biol. 1997; 17(3):1129-43. [PMID: 9032240]
  59. Prasad N., Topping RS. & Decker SJ. SH2-containing inositol 5′-phosphatase SHIP2 associates with the p130(Cas) adapter protein and regulates cellular adhesion and spreading. Mol. Cell. Biol. 2001; 21(4):1416-28. [PMID: 11158326]
  60. Berrier AL., Martinez R., Bokoch GM. & LaFlamme SE. The integrin beta tail is required and sufficient to regulate adhesion signaling to Rac1. J. Cell. Sci. 2002; 115(Pt 22):4285-91. [PMID: 12376560]
  61. Rottner K., Hall A. & Small JV. Interplay between Rac and Rho in the control of substrate contact dynamics. Curr. Biol. 1999; 9(12):640-8. [PMID: 10375527]
  62. Parsons JT., Horwitz AR. & Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat. Rev. Mol. Cell Biol. 2010; 11(9):633-43. [PMID: 20729930]
  63. Katoh H. & Negishi M. RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature 2003; 424(6947):461-4. [PMID: 12879077]
  64. Yu JA., Deakin NO. & Turner CE. Emerging role of paxillin-PKL in regulation of cell adhesion, polarity and migration. Cell Adh Migr; 4(3):342-7. [PMID: 20372092]
  65. Côté JF. & Vuori K. GEF what? Dock180 and related proteins help Rac to polarize cells in new ways. Trends Cell Biol. 2007; 17(8):383-93. [PMID: 17765544]
  66. Tachibana M., Kiyokawa E., Hara S., Iemura S., Natsume T., Manabe T. & Matsuda M. Ankyrin repeat domain 28 (ANKRD28), a novel binding partner of DOCK180, promotes cell migration by regulating focal adhesion formation. Exp. Cell Res. 2009; 315(5):863-76. [PMID: 19118547]
  67. Premont RT., Perry SJ., Schmalzigaug R., Roseman JT., Xing Y. & Claing A. The GIT/PIX complex: an oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors. Cell. Signal. 2004; 16(9):1001-11. [PMID: 15212761]
  68. Rosenberger G. & Kutsche K. AlphaPIX and betaPIX and their role in focal adhesion formation. Eur. J. Cell Biol. 2006; 85(3-4):265-74. [PMID: 16337026]
  69. Lim Y., Lim ST., Tomar A., Gardel M., Bernard-Trifilo JA., Chen XL., Uryu SA., Canete-Soler R., Zhai J., Lin H., Schlaepfer WW., Nalbant P., Bokoch G., Ilic D., Waterman-Storer C. & Schlaepfer DD. PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility. J. Cell Biol. 2008; 180(1):187-203. [PMID: 18195107]
  70. Guilluy C., Swaminathan V., Garcia-Mata R., O’Brien ET., Superfine R. & Burridge K. The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins. Nat. Cell Biol. 2011; 13(6):722-7. [PMID: 21572419]
  71. Kawasaki Y., Senda T., Ishidate T., Koyama R., Morishita T., Iwayama Y., Higuchi O. & Akiyama T. Asef, a link between the tumor suppressor APC and G-protein signaling. Science 2000; 289(5482):1194-7. [PMID: 10947987]
  72. Hildebrand JD., Taylor JM. & Parsons JT. An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase. Mol. Cell. Biol. 1996; 16(6):3169-78. [PMID: 8649427]
  73. Liu Y., Loijens JC., Martin KH., Karginov AV. & Parsons JT. The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly. Mol. Biol. Cell 2002; 13(6):2147-56. [PMID: 12058076]
  74. Katsumi A., Milanini J., Kiosses WB., del Pozo MA., Kaunas R., Chien S., Hahn KM. & Schwartz MA. Effects of cell tension on the small GTPase Rac. J. Cell Biol. 2002; 158(1):153-64. [PMID: 12105187]
  75. Sanz-Moreno V., Gadea G., Ahn J., Paterson H., Marra P., Pinner S., Sahai E. & Marshall CJ. Rac activation and inactivation control plasticity of tumor cell movement. Cell 2008; 135(3):510-23. [PMID: 18984162]
  76. Arthur WT. & Burridge K. RhoA inactivation by p190RhoGAP regulates cell spreading and migration by promoting membrane protrusion and polarity. Mol. Biol. Cell 2001; 12(9):2711-20. [PMID: 11553710]
  77. Tomar A., Lim ST., Lim Y. & Schlaepfer DD. A FAK-p120RasGAP-p190RhoGAP complex regulates polarity in migrating cells. J. Cell. Sci. 2009; 122(Pt 11):1852-62. [PMID: 19435801]
  78. Lamarche-Vane N. & Hall A. CdGAP, a novel proline-rich GTPase-activating protein for Cdc42 and Rac. J. Biol. Chem. 1998; 273(44):29172-7. [PMID: 9786927]
  79. Franco SJ. & Huttenlocher A. Regulating cell migration: calpains make the cut. J. Cell. Sci. 2005; 118(Pt 17):3829-38. [PMID: 16129881]
  80. Zimmermann P., Zhang Z., Degeest G., Mortier E., Leenaerts I., Coomans C., Schulz J., N’Kuli F., Courtoy PJ. & David G. Syndecan recycling [corrected] is controlled by syntenin-PIP2 interaction and Arf6. Dev. Cell 2005; 9(3):377-88. [PMID: 16139226]
  81. Boukerche H., Su ZZ., Prévot C., Sarkar D. & Fisher PB. mda-9/Syntenin promotes metastasis in human melanoma cells by activating c-Src. Proc. Natl. Acad. Sci. U.S.A. 2008; 105(41):15914-9. [PMID: 18832467]
  82. Baciu PC., Saoncella S., Lee SH., Denhez F., Leuthardt D. & Goetinck PF. Syndesmos, a protein that interacts with the cytoplasmic domain of syndecan-4, mediates cell spreading and actin cytoskeletal organization. J. Cell. Sci. 2000; 113 Pt 2:315-24. [PMID: 10633082]
  83. Tobe K., Sabe H., Yamamoto T., Yamauchi T., Asai S., Kaburagi Y., Tamemoto H., Ueki K., Kimura H., Akanuma Y., Yazaki Y., Hanafusa H. & Kadowaki T. Csk enhances insulin-stimulated dephosphorylation of focal adhesion proteins. Mol. Cell. Biol. 1996; 16(9):4765-72. [PMID: 8756634]
  84. Holt MR., Critchley DR. & Brindle NP. The focal adhesion phosphoprotein, VASP. Int. J. Biochem. Cell Biol. 1998; 30(3):307-11. [PMID: 9611773]
  85. Bretscher A., Edwards K. & Fehon RG. ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 2002; 3(8):586-99. [PMID: 12154370]
  86. Fehon RG., McClatchey AI. & Bretscher A. Organizing the cell cortex: the role of ERM proteins. Nat. Rev. Mol. Cell Biol. 2010; 11(4):276-87. [PMID: 20308985]
  87. Ohtsuka T., Nakanishi H., Ikeda W., Satoh A., Momose Y., Nishioka H. & Takai Y. Nexilin: a novel actin filament-binding protein localized at cell-matrix adherens junction. J. Cell Biol. 1998; 143(5):1227-38. [PMID: 9832551]
  88. Tran TC., Singleton C., Fraley TS. & Greenwood JA. Cysteine-rich protein 1 (CRP1) regulates actin filament bundling. BMC Cell Biol. 2005; 6:45. [PMID: 16336664]
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