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Paxillin LD4 Motif Binds PAK and PIX Through a Novel 95-kD Ankyrin Repeat, ARF-GAP Protein: A Role in Cytoskeletal Remodeling

Paxillin LD4 Motif Binds PAK and PIX Through a Novel 95-kD Ankyrin Repeat, ARF-GAP Protein: A Role in Cytoskeletal Remodeling

C E Turner, M C Brown, J A Perrotta, M C Riedy, S N Nikolopoulos, A R McDonald, S Bagrodia, S Thomas, P S Leventhal

J Cell Biol. 1999 May 17;145(4):851-63.

PMID: 10330411

Abstract:

Paxillin is a focal adhesion adaptor protein involved in the integration of growth factor- and adhesion-mediated signal transduction pathways. Repeats of a leucine-rich sequence named paxillin LD motifs (Brown M.C., M.S. Curtis, and C.E. Turner. 1998. Nature Struct. Biol. 5:677-678) have been implicated in paxillin binding to focal adhesion kinase (FAK) and vinculin. Here we demonstrate that the individual paxillin LD motifs function as discrete and selective protein binding interfaces. A novel scaffolding function is described for paxillin LD4 in the binding of a complex of proteins containing active p21 GTPase-activated kinase (PAK), Nck, and the guanine nucleotide exchange factor, PIX. The association of this complex with paxillin is mediated by a new 95-kD protein, p95PKL (paxillin-kinase linker), which binds directly to paxillin LD4 and PIX. This protein complex also binds to Hic-5, suggesting a conservation of LD function across the paxillin superfamily. Cloning of p95PKL revealed a multidomain protein containing an NH2-terminal ARF-GAP domain, three ankyrin-like repeats, a potential calcium-binding EF hand, calmodulin-binding IQ motifs, a myosin homology domain, and two paxillin-binding subdomains (PBS). Green fluorescent protein- (GFP-) tagged p95PKL localized to focal adhesions/complexes in CHO.K1 cells. Overexpression in neuroblastoma cells of a paxillin LD4 deletion mutant inhibited lamellipodia formation in response to insulin-like growth fac- tor-1. Microinjection of GST-LD4 into NIH3T3 cells significantly decreased cell migration into a wound. These data implicate paxillin as a mediator of p21 GTPase-regulated actin cytoskeletal reorganization through the recruitment to nascent focal adhesion structures of an active PAK/PIX complex potentially via interactions with p95PKL.

Chemicals Related in the Paper:

Catalog Number	Product Name	Price
IAR42411864	PAK1/CDC42, active, GST tagged human	Price
IAR42416179	FAK, active, GST tagged human	Price
IAR42416257	PAK1, active, GST tagged human	Price

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