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PMID: 9822598 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia.

The EMBO journal ·Vol. 17 ·No. 22 ·1998-11-16 ·Pages 6527-40

Abo A, Qu J, Cammarano MS, Dan C, Fritsch A, Baud V, Belisle B, Minden A

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.

MeSH Terms
Actins/metabolism Amino Acid Sequence Base Sequence Biopolymers Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Cycle Proteins/metabolism Cell Line Cytoskeleton/metabolism DNA, Complementary GTP-Binding Proteins/metabolism Golgi Apparatus/enzymology Guanosine Triphosphate/metabolism Humans JNK Mitogen-Activated Protein Kinases Jurkat Cells Mitogen-Activated Protein Kinases Molecular Sequence Data Mutation Phosphorylation Protein Binding Protein Serine-Threonine Kinases/genetics,metabolism Pseudopodia/metabolism Sequence Homology, Amino Acid Substrate Specificity cdc42 GTP-Binding Protein p21-Activated Kinases
Chemicals
Actins Biopolymers Cell Cycle Proteins DNA, Complementary Guanosine Triphosphate PAK4 protein, human Protein Serine-Threonine Kinases p21-Activated Kinases Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases GTP-Binding Proteins cdc42 GTP-Binding Protein
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Abo A
Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.
Qu J
Cammarano M S
Dan C
Fritsch A
Baud V
Belisle B
Minden A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.22.6527
Published
1998-11-16
Pages
6527-40
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171000
Subset
IM
Databases
GENBANK
AJ011855
External Links
PubMed source DOI: 10.1093/emboj/17.22.6527 PMC Full Text View journal details
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