Flowchart: Preparation: P130CAS


Text Box: Src

Text Box: Netrin-1





Text Box: p130CAS 

Axon signaling

Cell migration



Text Box: GTPase Text Box: Rac1

Text Box: Cdc42




Brain Res. 2006 Jan 5;1067(1):170-6. Epub 2005 Dec 15.

Related Articles, Links

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J Neurosci. 2007 Jan 24;27(4):957-68.Click here to read  Links

p130CAS is required for netrin signaling and commissural axon guidance.

P     Liu G, Li W, Gao X, Li X, Jurgensen C, Park HT, Shin NY, Yu J, He ML, Hanks SK, Wu JY, Guan KL, Rao Y.

Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

Netrins are an important family of axon guidance cues. Here, we report that netrin-1 induces tyrosine phosphorylation of p130(CAS) (Crk-associated substrate). Our biochemical studies indicate that p130(CAS) is downstream of the Src family kinases and upstream of the small GTPase Rac1 and Cdc42. Inhibition of p130(CAS) signaling blocks both the neurite outgrowth-promoting activity and the axon attraction activity of netrin-1. p130(CAS) RNA interference inhibits the attraction of commissural axons in the spinal cord by netrin-1 and causes defects in commissural axon projection in the embryo. These results demonstrate that p130(CAS) is a key component in the netrin signal transduction pathway and plays an important role in guiding commissural axons in vivo.

PMID: 17251438 [PubMed - indexed for MEDLINE]

J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12.Click here to read  Links

Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas.

P     Modzelewska K, Newman LP, Desai R, Keely PJ.

Department of Pharmacology and Molecular and Cellular Pharmacology Program, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.

We previously showed that activation of the small GTPase Cdc42 promotes breast cell migration on a collagen matrix. Here we further define the signaling pathways that drive this response and show that Cdc42-mediated migration relies on the adaptor molecule p130(Cas). Activated Cdc42 enhanced p130(Cas) phosphorylation and its binding to Crk. Cdc42-driven migration and p130(Cas) phosphorylation were dependent on the Cdc42 effector Ack1 (activated Cdc42-associated kinase). Ack1 formed a signaling complex that also included Cdc42, p130(Cas), and Crk, formation of which was regulated by collagen stimulation. The interaction between Ack1 and p130(Cas) occurred through their respective SH3 domains, while the substrate domain of p130(Cas) was the major site of Ack1-dependent phosphorylation. Signaling through this complex is functionally relevant, because treatment with either p130(Cas) or Ack1 siRNA blocked Cdc42-induced migration. These results suggest that Cdc42 exerts its effects on cell migration in part through its effector Ack1, which regulates p130(Cas) signaling.

PMID: 17038317 [PubMed - indexed for MEDLINE