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Cytoskeleton remodeling_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 ].
Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S
Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase.
Science (New York, N.Y.) 1999 Aug 6;285(5429):895-8
Riento K, Ridley AJ
Rocks: multifunctional kinases in cell behaviour.
Nature reviews. Molecular cell biology 2003 Jun;4(6):446-56
Pfitzer G
Invited review: regulation of myosin phosphorylation in smooth muscle.
Journal of applied physiology (Bethesda, Md. : 1985) 2001 Jul;91(1):497-503
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
Sanders LC, Matsumura F, Bokoch GM, de Lanerolle P
Inhibition of myosin light chain kinase by p21-activated kinase.
Science (New York, N.Y.) 1999 Mar 26;283(5410):2083-5
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p21-activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts.
The Journal of cell biology 1999 May 17;145(4):837-49
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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
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
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
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Molecular mechanisms controlling actin filament dynamics in nonmuscle cells.
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Motility determinants in WASP family proteins.
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