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Protein tyrosine phosphatase activity is necessary for E‐cadherin‐activated Src signaling
Author(s) -
McLachlan Robert W.,
Yap Alpha S.
Publication year - 2011
Publication title -
cytoskeleton
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.95
H-Index - 86
eISSN - 1949-3592
pISSN - 1949-3584
DOI - 10.1002/cm.20492
Subject(s) - microbiology and biotechnology , proto oncogene tyrosine protein kinase src , biology , cadherin , protein tyrosine phosphatase , adherens junction , actin cytoskeleton , signal transduction , myosin , cytoskeleton , biochemistry , cell
Abstract Co‐operation between cadherin adhesion molecules and the cytoskeleton is a key aspect of tissue morphogenesis that is mediated by cortical signaling at adhesive junctions. One such signal is the non‐receptor tyrosine kinase, Src, which acts in several pathways at epithelial junctions, including E‐cadherin signaling itself. We now present two new insights into junctional Src signaling. Firstly, we report that upstream protein tyrosine phosphatase (PTP) activity is required to stimulate E‐cadherin‐activated Src signaling at junctions. Perturbing PTP activity with vanadate selectively reduced the activity of Src tyrosine kinases at junctions. Moreover, E‐cadherin homophilic ligation could not stimulate Src signaling in vanadate‐treated cells. Additionally, vanadate treatment phenocopied the effects of Src inhibition on the actin cytoskeleton, suggesting that PTP activity is required for the dynamic regulation of the actin cytoskeleton by cadherin‐activated Src signaling. Secondly, we identified a role for PTP‐activated Src signaling in supporting apical junctional tension by targeting non‐muscle myosin IIB. The linear shape of the apical junctions was lost in PTP‐ and Src‐inhibited cells, and inhibiting Src selectively affected the junctional localization of myosin IIB but not of myosin IIA. We conclude that PTP‐activated Src signaling is a possible upstream regulator of myosin IIB at the epithelial zonula adherens. © 2010 Wiley‐Liss, Inc.