Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The roles of P21-activated kinase (PAK) in the regulation of axon outgrowth downstream of extracellular matrix (ECM) proteins are poorly understood. Here we show that PAK1-3 and PIX are expressed in the developing spinal cord and differentially localize to point contacts and filopodial tips within motile growth cones. Using a specific interfering peptide called PAK18, we found that axon outgrowth is robustly stimulated on laminin by partial inhibition of PAK-PIX interactions and PAK function, whereas complete inhibition of PAK function stalls axon outgrowth. Furthermore, modest inhibition of PAK-PIX stimulates the assembly and turnover of growth cone point contacts, whereas strong inhibition over-stabilizes adhesions. Point mutations within PAK confirm the importance of PIX binding. Together our data suggest that regulation of PAK-PIX interactions in growth cones controls neurite outgrowth by influencing the activity of several important mediators of actin filament polymerization and retrograde flow, as well as integrin-dependent adhesion to laminin.
Aizawa,
Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse.
2001, Pubmed
Aizawa,
Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse.
2001,
Pubmed
Ang,
Dock and Pak regulate olfactory axon pathfinding in Drosophila.
2003,
Pubmed
Arias-Romero,
A tale of two Paks.
2008,
Pubmed
Bagrodia,
A novel regulator of p21-activated kinases.
1998,
Pubmed
Bisson,
EphA4 signaling regulates blastomere adhesion in the Xenopus embryo by recruiting Pak1 to suppress Cdc42 function.
2007,
Pubmed
,
Xenbase
Bisson,
The catalytic domain of xPAK1 is sufficient to induce myosin II dependent in vivo cell fragmentation independently of other apoptotic events.
2003,
Pubmed
,
Xenbase
Bito,
A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons.
2000,
Pubmed
Boda,
The mental retardation protein PAK3 contributes to synapse formation and plasticity in hippocampus.
2004,
Pubmed
Bokoch,
Biology of the p21-activated kinases.
2003,
Pubmed
Bowes,
Xenbase: gene expression and improved integration.
2010,
Pubmed
,
Xenbase
Bright,
PAK1 and PAK2 have different roles in HGF-induced morphological responses.
2009,
Pubmed
Brown,
Paxillin-dependent paxillin kinase linker and p21-activated kinase localization to focal adhesions involves a multistep activation pathway.
2002,
Pubmed
Carlstrom,
Bidirectional remodeling of β1-integrin adhesions during chemotropic regulation of nerve growth.
2011,
Pubmed
,
Xenbase
Cau,
Regulation of Xenopus p21-activated kinase (X-PAK2) by Cdc42 and maturation-promoting factor controls Xenopus oocyte maturation.
2000,
Pubmed
,
Xenbase
Chan,
Traction dynamics of filopodia on compliant substrates.
2008,
Pubmed
Chien,
Navigational errors made by growth cones without filopodia in the embryonic Xenopus brain.
1993,
Pubmed
,
Xenbase
Cobos,
Dlx transcription factors promote migration through repression of axon and dendrite growth.
2007,
Pubmed
Daniels,
Membrane targeting of p21-activated kinase 1 (PAK1) induces neurite outgrowth from PC12 cells.
1998,
Pubmed
Deakin,
Paxillin comes of age.
2008,
Pubmed
Dent,
GAP-43 phosphorylation is dynamically regulated in individual growth cones.
1992,
Pubmed
Dent,
The growth cone cytoskeleton in axon outgrowth and guidance.
2011,
Pubmed
Fan,
Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline.
2003,
Pubmed
Galbraith,
Polymerizing actin fibers position integrins primed to probe for adhesion sites.
2007,
Pubmed
Godement,
Retinal axon divergence in the optic chiasm: dynamics of growth cone behavior at the midline.
1994,
Pubmed
Gómez,
Working with Xenopus spinal neurons in live cell culture.
2003,
Pubmed
,
Xenbase
Hayashi,
Pak1 is involved in dendrite initiation as a downstream effector of Rac1 in cortical neurons.
2002,
Pubmed
Heckman,
Relationship of p21-activated kinase (PAK) and filopodia to persistence and oncogenic transformation.
2009,
Pubmed
Hines,
Asymmetric endocytosis and remodeling of beta1-integrin adhesions during growth cone chemorepulsion by MAG.
2010,
Pubmed
,
Xenbase
Hing,
Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila.
1999,
Pubmed
Hitchcock,
Actin deoxyroboncuclease I interaction. Depolymerization and nucleotide exchange.
1980,
Pubmed
Ichetovkin,
Cofilin produces newly polymerized actin filaments that are preferred for dendritic nucleation by the Arp2/3 complex.
2002,
Pubmed
Kayser,
EphB receptors couple dendritic filopodia motility to synapse formation.
2008,
Pubmed
Keren,
Mechanism of shape determination in motile cells.
2008,
Pubmed
Kim,
Isolation of Rho GTPase effector pathways during axon development.
2003,
Pubmed
Kolodkin,
Mechanisms and molecules of neuronal wiring: a primer.
2011,
Pubmed
Kreis,
PAK signalling in neuronal physiology.
2009,
Pubmed
Kuo,
Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation.
2011,
Pubmed
Loudon,
RhoA-kinase and myosin II are required for the maintenance of growth cone polarity and guidance by nerve growth factor.
2006,
Pubmed
Lowery,
The trip of the tip: understanding the growth cone machinery.
2009,
Pubmed
,
Xenbase
Lucanic,
The Caenorhabditis elegans P21-activated kinases are differentially required for UNC-6/netrin-mediated commissural motor axon guidance.
2006,
Pubmed
Manser,
PAK kinases are directly coupled to the PIX family of nucleotide exchange factors.
1998,
Pubmed
Marín,
Guiding neuronal cell migrations.
2010,
Pubmed
Marler,
Outgrowth of neurites from NIE-115 neuroblastoma cells is prevented on repulsive substrates through the action of PAK.
2005,
Pubmed
Marsick,
Activation of ezrin/radixin/moesin mediates attractive growth cone guidance through regulation of growth cone actin and adhesion receptors.
2012,
Pubmed
Marsick,
Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1.
2010,
Pubmed
,
Xenbase
Maruta,
Interfering with Ras signaling using membrane-permeable peptides or drugs.
2002,
Pubmed
Myers,
Focal adhesion kinase promotes integrin adhesion dynamics necessary for chemotropic turning of nerve growth cones.
2011,
Pubmed
,
Xenbase
Myers,
Focal adhesion kinase modulates Cdc42 activity downstream of positive and negative axon guidance cues.
2012,
Pubmed
,
Xenbase
Myers,
Regulation of axonal outgrowth and pathfinding by integrin-ECM interactions.
2011,
Pubmed
Nayal,
Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics.
2006,
Pubmed
Obermeier,
PAK promotes morphological changes by acting upstream of Rac.
1998,
Pubmed
Petchprayoon,
Fluorescent kabiramides: new probes to quantify actin in vitro and in vivo.
2005,
Pubmed
Raymond,
X linked mental retardation: a clinical guide.
2006,
Pubmed
Robles,
Src-dependent tyrosine phosphorylation at the tips of growth cone filopodia promotes extension.
2005,
Pubmed
,
Xenbase
Robles,
Focal adhesion kinase signaling at sites of integrin-mediated adhesion controls axon pathfinding.
2006,
Pubmed
,
Xenbase
Rosenberger,
AlphaPIX and betaPIX and their role in focal adhesion formation.
2006,
Pubmed
Rozen,
Primer3 on the WWW for general users and for biologist programmers.
2000,
Pubmed
Santiago-Medina,
Imaging adhesion and signaling dynamics in Xenopus laevis growth cones.
2012,
Pubmed
,
Xenbase
Sarmiere,
Regulation of the neuronal actin cytoskeleton by ADF/cofilin.
2004,
Pubmed
Shafer,
Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance.
2011,
Pubmed
Shekarabi,
Deleted in colorectal cancer binding netrin-1 mediates cell substrate adhesion and recruits Cdc42, Rac1, Pak1, and N-WASP into an intracellular signaling complex that promotes growth cone expansion.
2005,
Pubmed
Souopgui,
XPak3 promotes cell cycle withdrawal during primary neurogenesis in Xenopus laevis.
2002,
Pubmed
,
Xenbase
Sretavan,
Time-lapse video analysis of retinal ganglion cell axon pathfinding at the mammalian optic chiasm: growth cone guidance using intrinsic chiasm cues.
1993,
Pubmed
Stofega,
Constitutive p21-activated kinase (PAK) activation in breast cancer cells as a result of mislocalization of PAK to focal adhesions.
2004,
Pubmed
Tanaka,
Biomolecular mimicry in the actin cytoskeleton: mechanisms underlying the cytotoxicity of kabiramide C and related macrolides.
2003,
Pubmed
ten Klooster,
Targeting and activation of Rac1 are mediated by the exchange factor beta-Pix.
2006,
Pubmed
Turner,
Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling.
1999,
Pubmed
Wiggan,
ADF/cofilin regulates actomyosin assembly through competitive inhibition of myosin II binding to F-actin.
2012,
Pubmed
Woo,
Rac1 and RhoA promote neurite outgrowth through formation and stabilization of growth cone point contacts.
2006,
Pubmed
,
Xenbase
Woo,
Retinotopic mapping requires focal adhesion kinase-mediated regulation of growth cone adhesion.
2009,
Pubmed
,
Xenbase
Wu,
Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but is dispensable for chemotaxis.
2012,
Pubmed
Zaidel-Bar,
The switchable integrin adhesome.
2010,
Pubmed
Zaidel-Bar,
A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions.
2007,
Pubmed
Zhang,
A GIT1/PIX/Rac/PAK signaling module regulates spine morphogenesis and synapse formation through MLC.
2005,
Pubmed
Zhao,
Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease.
2006,
Pubmed
