FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5.

Abstract:

:During neuronal development, netrin and its receptors UNC5 and DCC (deleted in colorectal cancer) guide axonal growth cones in navigating to their targets. Netrin also plays important roles in the regulation of cell migration, tissue morphogenesis and tumor growth. Here, we show that netrin induces UNC5 tyrosine phosphorylation and that this effect of netrin is dependent on its co-receptor DCC. UNC5 tyrosine phosphorylation is known to be important for netrin to induce cell migration and axonal repulsion. Src tyrosine kinase activity is required for netrin to stimulate UNC5 tyrosine phosphorylation in neurons and transfected cells. The SH2 domain of Src kinase directly interacts with the cytosolic domain of UNC5 in a tyrosine-phosphorylation-dependent manner. Furthermore, the tyrosine kinase focal adhesion kinase (FAK) is also involved in netrin-induced UNC5 tyrosine phosphorylation. Both Src and FAK can phosphorylate UNC5. Our data suggest a model in which netrin stimulates UNC5 tyrosine phosphorylation and signaling in a manner dependent on the co-receptor DCC, through the recruitment of Src and FAK kinases.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Li W,Aurandt J,Jürgensen C,Rao Y,Guan KL

doi

10.1242/jcs.02697

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

47-55

issue

Pt 1

eissn

0021-9533

issn

1477-9137

pii

119/1/47

journal_volume

119

pub_type

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