Pathway maps

Cytoskeleton remodeling_CDC42 in cellular processes
Cytoskeleton remodeling_CDC42 in cellular processes

Object List (links open in MetaCore):

PAK1, COPG2, CEP3, Arp2/3, CDC42, Destrin, LIMK2, c-Raf-1, Actin cytoskeletal, PAK3, N-WASP, MLK3(MAP3K11), PKC-zeta, PARD6, CEP2, LIMK1, Cofilin, WASP, PAK2, SPEC1, MRCKalpha, PAK4


CDC42 in cellular processes

Cell division cycle 42 ( CDC42 ) is a member of the RAS superfamily of small GTPases and plays an essential role in control of cell polarity, actin cytoskeleton rearrangements, protein trafficking and directed cell movements in a vide variety of mammalian cells [1], [2], [3], [4]. CDC42 is activated by GEFs (Guanine Nucleotide Exchange Factors), and repressed by GAPs (GTPase- Activating Proteins).

GTP-bound CDC42 activates a large number of effector proteins and promotes different signaling pathways. p21 protein (Cdc42/Rac)-activated kinases 1-4 ( PAK1, PAK2, PAK3, PAK4 ) are known downstream targets of CDC42 [5], [6]. The association between the active GTP form of CDC42 and the PBD domain of PAK1-4 promotes PAK1-4 autophosphorylation [7]. All four PAKs are capable to promote Mitogen-activated protein kinases 8-10 ( JNK (MAPK 8-10) ) signaling activation that leads to cytoskeletal rearrangements and cell motility [8].

CDC42 can activate JNK pathway also by binding and stimulation of Mitogen-activated protein kinase kinase kinase 11 ( MLK3(MAP3K11) ) [9].

Binding of CDC42 small effector 1 ( SPEC1 ) to CDC42 suppresses CDC42 -induced JNK activation and cytoskeleton remodeling [10], [11].

CDC42 promotes changes in actin cytoskeleton by several pathways. CDC42 activates PAK1, PAK4 and CDC42 binding protein kinase alpha ( MRCKalpha ) which phosphorylate LIM domain kinases 1 and 2 ( LIMK1 and LIMK2 ) and they subsequently phosphorylate and inhibit Cofilin and Destrin (actin depolymerizing factor) ( Destrin ). This leads to actin polymerization and stimulation of filopodia and stress fibers formation [12], [13], [3], [14].

PAK3 stimulated by CDC42 induces v-raf-1 murine leukemia viral oncogene homolog 1 ( c-Raf-1 ) signaling [15].

CDC42 induces actin cytoskeleton changes also by activating Wiskott-Aldrich syndrome ( WASP ) and Wiskott-Aldrich syndrome-like ( N-WASP ) [16], [17], which binds to Actin related protein 2/3 complex ( Arp2/3 ) and this leads to Actin cytoskeletal polymerization and filopodia formation [18], [19].

And finally, CDC42 promotes cytoskeleton remodeling by binding to CDC42 effector proteins 2 and 3 ( CEP2 and CEP3 ) [20], [21].

CDC42 can directly bind to Par-6 partitioning defective 6 homolog ( PARD6 ) which activates Protein kinase C, zeta ( PKC-zeta ), and this leads to establishment of cell polarity and promotes cellular transformation [22], [23], [24]. Also CDC42 induces cellular transformation by associating with the Coatomer protein complex, subunit gamma 2 ( COPG2 ) [25].


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