title: PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia.
abstract: The GTPases Rac and Cdc42Hs control diverse cellular functions. In addition to being mediators of intracellular signaling cascades, they have important roles in cell morphogenesis and mitogenesis. We have identified a novel PAK-related kinase, PAK4, as a new effector molecule for Cdc42Hs. PAK4 interacts only with the activated form of Cdc42Hs through its GTPase-binding domain (GBD). Co-expression of PAK4 and the constitutively active Cdc42HsV12 causes the redistribution of PAK4 to the brefeldin A-sensitive compartment of the Golgi membrane and the subsequent induction of filopodia and actin polymerization. Importantly, the reorganization of the actin cytoskeleton is dependent on PAK4 kinase activity and on its interaction with Cdc42Hs. Thus, unlike other members of the PAK family, PAK4 provides a novel link between Cdc42Hs and the actin cytoskeleton. The cellular locations of PAK4 and Cdc42Hs suggest a role for the Golgi in cell morphogenesis.
authors.affiliation: Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.
authors.forename: A
authors.initials: A
authors.lastname: Abo
authors.forename: J
authors.initials: J
authors.lastname: Qu
authors.forename: M S
authors.initials: MS
authors.lastname: Cammarano
authors.forename: C
authors.initials: C
authors.lastname: Dan
authors.forename: A
authors.initials: A
authors.lastname: Fritsch
authors.forename: V
authors.initials: V
authors.lastname: Baud
authors.forename: B
authors.initials: B
authors.lastname: Belisle
authors.forename: A
authors.initials: A
authors.lastname: Minden
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001704:Biopolymers; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000201:enzymology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D020764:cdc42 GTP-Binding Protein; D054462:p21-Activated Kinases
chemical_list: D000199:Actins; D001704:Biopolymers; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D006160:Guanosine Triphosphate; C116367:PAK4 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein