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Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling

Dynamic modulation of cell adhesion is integral to a wide range of biological processes. The small guanosine triphosphatase (GTPase) Rap1 is an important regulator of cell–cell and cell–matrix adhesions. We show here that induced expression of activated Abl tyrosine kinase reduces Rap1-GTP levels th...

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Detalles Bibliográficos
Autores principales: Huang, XiaoDong, Wu, Diana, Jin, Hua, Stupack, Dwayne, Wang, Jean Y.J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582888/
https://www.ncbi.nlm.nih.gov/pubmed/19001122
http://dx.doi.org/10.1083/jcb.200801192
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author Huang, XiaoDong
Wu, Diana
Jin, Hua
Stupack, Dwayne
Wang, Jean Y.J.
author_facet Huang, XiaoDong
Wu, Diana
Jin, Hua
Stupack, Dwayne
Wang, Jean Y.J.
author_sort Huang, XiaoDong
collection PubMed
description Dynamic modulation of cell adhesion is integral to a wide range of biological processes. The small guanosine triphosphatase (GTPase) Rap1 is an important regulator of cell–cell and cell–matrix adhesions. We show here that induced expression of activated Abl tyrosine kinase reduces Rap1-GTP levels through phosphorylation of Tyr221 of CrkII, which disrupts interaction of CrkII with C3G, a guanine nucleotide exchange factor for Rap1. Abl-dependent down-regulation of Rap1-GTP causes cell rounding and detachment only when the Rho–ROCK1 pathway is also activated, for example, by lysophosphatidic acid (LPA). During ephrin-A1–induced retraction of PC3 prostate cancer cells, we show that endogenous Abl is activated and disrupts the CrkII–C3G complex to reduce Rap1-GTP. Interestingly, ephrin-A1–induced PC3 cell retraction also requires LPA, which stimulates Rho to a much higher level than that is activated by ephrin-A1. Our results establish Rap1 as another downstream target of the Abl–CrkII signaling module and show that Abl–CrkII collaborates with Rho–ROCK1 to stimulate cell retraction.
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spelling pubmed-25828882009-05-18 Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling Huang, XiaoDong Wu, Diana Jin, Hua Stupack, Dwayne Wang, Jean Y.J. J Cell Biol Research Articles Dynamic modulation of cell adhesion is integral to a wide range of biological processes. The small guanosine triphosphatase (GTPase) Rap1 is an important regulator of cell–cell and cell–matrix adhesions. We show here that induced expression of activated Abl tyrosine kinase reduces Rap1-GTP levels through phosphorylation of Tyr221 of CrkII, which disrupts interaction of CrkII with C3G, a guanine nucleotide exchange factor for Rap1. Abl-dependent down-regulation of Rap1-GTP causes cell rounding and detachment only when the Rho–ROCK1 pathway is also activated, for example, by lysophosphatidic acid (LPA). During ephrin-A1–induced retraction of PC3 prostate cancer cells, we show that endogenous Abl is activated and disrupts the CrkII–C3G complex to reduce Rap1-GTP. Interestingly, ephrin-A1–induced PC3 cell retraction also requires LPA, which stimulates Rho to a much higher level than that is activated by ephrin-A1. Our results establish Rap1 as another downstream target of the Abl–CrkII signaling module and show that Abl–CrkII collaborates with Rho–ROCK1 to stimulate cell retraction. The Rockefeller University Press 2008-11-17 /pmc/articles/PMC2582888/ /pubmed/19001122 http://dx.doi.org/10.1083/jcb.200801192 Text en © 2008 Huang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Huang, XiaoDong
Wu, Diana
Jin, Hua
Stupack, Dwayne
Wang, Jean Y.J.
Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling
title Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling
title_full Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling
title_fullStr Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling
title_full_unstemmed Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling
title_short Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling
title_sort induction of cell retraction by the combined actions of abl–crkii and rho–rock1 signaling
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582888/
https://www.ncbi.nlm.nih.gov/pubmed/19001122
http://dx.doi.org/10.1083/jcb.200801192
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