Abl tyrosine kinases modulate cadherin-dependent adhesion upstream and downstream of Rho family GTPases

Formation and dissolution of intercellular adhesions are processes of paramount importance during tissue morphogenesis and for pathological conditions such as tumor metastasis. Cadherin-mediated intercellular adhesion requires dynamic regulation of the actin cytoskeleton. The pathways that link cadh...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2008-02, Vol.7 (4), p.444-448
Main Authors: Zandy, Nicole L., Pendergast, Ann Marie
Format: Article
Language:English
Subjects:
Actins - metabolism
Adherens Junctions - metabolism
Binding
Biology
Bioscience
Cadherins - metabolism
Calcium
Cancer
Cell
Cycle
Cytoskeleton - metabolism
Landes
Models, Biological
Organogenesis
Proteins
Proto-Oncogene Proteins c-abl - metabolism
rho GTP-Binding Proteins - metabolism
Signal Transduction - physiology
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Summary:Formation and dissolution of intercellular adhesions are processes of paramount importance during tissue morphogenesis and for pathological conditions such as tumor metastasis. Cadherin-mediated intercellular adhesion requires dynamic regulation of the actin cytoskeleton. The pathways that link cadherin signaling to cytoskeletal regulation remain poorly defined. We have recently uncovered a novel role for the Abl family of tyrosine kinases linking cadherin-mediated adhesion to actin dynamics via the regulation of Rho family GTPases. Abl kinases are activated by cadherin engagement, localize to cell-cell junctions, and are required for the formation of adherens junctions. Notably, we showed that Abl kinases are required for Rac activation during formation of adherens junctions, and also regulate a Rho-ROCK-myosin signaling pathway that is required for the maintenance of intercellular adhesion. Here we show that Abl kinases regulate the formation and strengthening of adherens junctions downstream of active Rac, and that Abl tyrosine kinases are components of a positive feed-back loop that employs the Crk/CrkL adaptor proteins to promote the formation and maturation of adherens junctions.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.7.4.5452