Pathway maps

Cytoskeleton remodeling_Regulation of actin cytoskeleton by Rho GTPases
Cytoskeleton remodeling_Regulation of actin cytoskeleton by Rho GTPases

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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    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
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    WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. The EMBO journal 1998 Dec 1;17(23):6932-41
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    Motility determinants in WASP family proteins. Molecular biology of the cell 2002 Nov;13(11):4045-59