Positional Control of Cell Fate Through Joint Integrin/Receptor Protein Kinase Signaling

Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Annual Review of Cell and Developmental Biology (Impact Factor: 20.24). 01/2003; 19:173-206. DOI: 10.1146/annurev.cellbio.19.031103.133334
Source: PubMed

ABSTRACT Cells adhere to the extracellular matrix throughout most of their lifetime. This close, intimate contact with the matrix exerts an extraordinary control on the behavior of cells, determining whether they move or stay put, proliferate or remain quiescent, and even live or die. Attachment to the matrix not only enables cells to respond to soluble growth factors and cytokines but also determines the nature of the response. The integrins are a large family of receptors that attach cells to the matrix, organize their cytoskeleton, and cooperate with receptor protein tyrosine kinases to regulate cell fate. Research on integrin signaling is beginning to explain the complex and specific effects that the extracellular matrix exerts on cells.

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    • "Besides controlling GF bioavailability, the ECM also modulates GF signaling through the interplay between GFs, ECM proteins, cell-adhesion receptors, and GF receptors (Giancotti and Tarone, 2003; Hynes, 2009; Kim et al., 2011). For example, the binding of VEGF 165 to fibronectin forms molecular complexes that induce the formation of clusters between VEGF receptor and integrins (Wijelath et al., 2006; Martino et al., 2011, 2013). "
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    ABSTRACT: Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis onVEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.
    Frontiers in Bioengineering and Biotechnology 04/2015; 3(45). DOI:10.3389/fbioe.2015.00045
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    • "Adhesion by integrin-mediated junctions allows tissues to withstand mechanical load and is essential for tissue integrity. Integrinbased signalling regulates cell migration, division, and differentiation (Bokel and Brown, 2002; Giancotti and Tarone, 2003; Meighan and Schwarzbauer, 2008). Thus, integrins are the major family of cell surface receptors that mediate cell attachment to the extracellular matrix and can mediate cell– cell interactions (Hynes, 1992; Hynes 1999; Li and Sakaguchi, 2002). "
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    ABSTRACT: How the neural retina is held in its place in the human physiological living body) Bratislava 2014 Original self-publishing first edition of the monograph, entitled " Gergely's retinal linkage (How the neural retina is held in its place in the human physiological living body) " by Gergely K (contact:; affiliation: Faculty of Medicine in Bratislava, Comenius University in Bratislava, Slovak Republic; This work may not be translated or copied in whole or in part without the written permission of the publisher Květoslava Gergelyova, MD; Prague, Czech Republic (contact:, except for brief excerpts in connection with scientific articles or scholarly analysis [regular citation: Gergely K. Gergely's retinal linkage (How the neural retina is held in its place in the human physiological living body). Publisher Gergelyova, 2014]. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.
    1. 12/2014; Gergelyova Kvetoslava,, ISBN: 978-80-260-6819-8
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    • ", 1999 , 1993 ) . In vitro , multiple studies demonstrated that FN binds α5β1 and stimulates α5β1 signaling , activating pathways regulat - ing cell proliferation , survival , migration , remodeling of actin cytoskeleton and others ( Giancotti and Tarone , 2003 ; Schwartz and Assoian , 2001 ) . In vivo , a major role for integrin α5β1 as a FN receptor is supported by gene knock out studies , which showed that the phenotype of integrin α5 - null embryos is similar to that of FN - nulls ( Mittal et al . "
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    ABSTRACT: Fibronectin and its major receptor, integrin α5β1 are required for embryogenesis. These mutants have similar phenotypes, although, defects in integrin α5-deficient mice are milder. In this paper, we examined heart development in those mutants, in which the heart is formed, and discovered that both fibronectin and integrin α5 were required for cardiac morphogenesis, and in particular, for the formation of the cardiac outflow tract. We found that Isl1(+) precursors are specified and migrate into the heart in fibronectin- or integrin α5-mutant embryos, however, the hearts in these mutants are of aberrant shape, and the cardiac outflow tracts are short and malformed. We show that these defects are likely due to the requirement for cell adhesion to fibronectin for proliferation of myocardial progenitors and for Fgf8 signaling in the pharyngeal region.
    Developmental Biology 06/2013; 381(1). DOI:10.1016/j.ydbio.2013.06.010 · 3.64 Impact Factor
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