Pathway Map Details

Cytoskeleton remodeling_Regulation of actin cytoskeleton by Rho GTPases

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Object list (links open in MetaCore):

RhoA, Arp2/3, Myosin II, MLCK, Rac1, Fascin, MLCP (reg), MLCP (cat), MyHC, MRLC, MELC, WASF1(WAVE1), PAK1, LIMK1, ROCK, WASP, Filamin A, Actin cytoskeletal, Cofilin, CDC42, Actin, LIMK2, Profilin


Regulation of actin cytoskeleton by Rho GTPases

Ras homolog gene family, member A ( RhoA ) downstream effector Rho-associated, coiled-coil containing protein kinase ( ROCK ) directly phosphorylates LIM domain kinases 1 and 2 ( LIMK1 and LIMK2 ) that in turn phosphorylates Cofilin. Cofilin exhibits Actin -depolymerizing activity followed by reorganization of the Actin cytoskeleton [1].

The activated ROCK also subsequently phosphorylates and inactivates the Myosin light chain phosphatase ( MLCP ) [2] that attenuates Myosin light chains ( MELC ) (myosin light chains) and Myosin light chain regulatory ( MRLC ) phosphorylation [3].

Ras-related C3 botulinum toxin substrate 1 ( Rac1 ) downstream effector P21 protein-activated kinase 1 ( PAK1 ) directly phosphorylates LIMK1 [4], inhibits MLCK [5], activates MRLC [6] and ARP2 actin-related protein 2 and 3 ( Arp2/3 ) complex [7]. Arp2/3 complex nucleates new Actin filaments from the sides of preexisting filaments. [8]. Also, WAS protein family member 1 ( WAVE ) plays a critical role downstream of Rac in that it regulates the Actin cytoskeleton required for membrane ruffling. WAVE share function as an inducer of Actin reorganization through profiling [9].

Cell division cycle 42 ( CDC42 ) initiates Wiskott-Aldrich syndrome ( WASP )/ Arp2/3 nucleation of Actin [10]. Recruitment of factors, including Profilin, by WASP stimulates cellular Actin -based motility [11].


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    Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 1999 Aug 6;285(5429):895-8
  2. Riento K, Ridley AJ
    Rocks: multifunctional kinases in cell behaviour. Nature reviews. Molecular cell biology. 2003 Jun;4(6):446-56
  3. Pfitzer G
    Invited review: regulation of myosin phosphorylation in smooth muscle. Journal of applied physiology (Bethesda, Md. : 1985) 2001 Jul;91(1):497-503
  4. Edwards DC, Sanders LC, Bokoch GM, Gill GN
    Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nature cell biology 1999 Sep;1(5):253-9
  5. Sanders LC, Matsumura F, Bokoch GM, de Lanerolle P
    Inhibition of myosin light chain kinase by p21-activated kinase. Science 1999 Mar 26;283(5410):2083-5
  6. Sells MA, Boyd JT, Chernoff J
    p21-activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts. The Journal of cell biology 1999 May 17;145(4):837-49
  7. Vadlamudi RK, Li F, Barnes CJ, Bagheri-Yarmand R, Kumar R
    p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate. EMBO reports 2004 Feb;5(2):154-60
  8. Dayel MJ, Mullins RD
    Activation of Arp2/3 complex: addition of the first subunit of the new filament by a WASP protein triggers rapid ATP hydrolysis on Arp2. PLoS biology 2004 Apr;2(4):E91
  9. Miki H, Suetsugu S, Takenawa T
    WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. The EMBO journal 1998 Dec 1;17(23):6932-41
  10. Pollard TD, Blanchoin L, Mullins RD
    Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annual review of biophysics and biomolecular structure 2000;29:545-76
  11. Yarar D, D'Alessio JA, Jeng RL, Welch MD
    Motility determinants in WASP family proteins. Molecular biology of the cell 2002 Nov;13(11):4045-59