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Matrix‐specific activation of Src and Rho initiates capillary morphogenesis of endothelial cells
Author(s) -
Liu Yanqiu,
Senger Donald R.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0948com
Subject(s) - microbiology and biotechnology , morphogenesis , proto oncogene tyrosine protein kinase src , integrin , extracellular matrix , stress fiber , endothelial stem cell , laminin , chemistry , angiogenesis , biology , cell , focal adhesion , kinase , signal transduction , biochemistry , cancer research , in vitro , gene
Interstitial collagen I stimulates micro¬vascular endothelial cells to form solid cords that imitate precapillary structures found during angiogenesis. Time‐lapse microscopy identified cell retraction and disruption of cell–cell contacts as early critical steps in collagen I‐induced capillary morphogenesis. These early stages paralleled collagen I activation of Src kinase and GTPase Rho through βl integrins. The Src inhibitor PP2, dominant‐negative Src, and Rho inhibitor exoenzyme C3 transferase each inhibited col¬lagen I induction of actin stress fibers that mediate cell retraction and each inhibited capillary morphogenesis. Collagen I also disrupted VE‐cadherin from intercellu¬lar junctions through a Src‐dependent mechanism;both the Src inhibitor PP2 and dominant‐negative Src pre¬served VE‐cadherin localization to regions of cell‐cell contact. An active Src mutant disrupted VE‐cadherin and cell–cell contacts similarly to collagen I. In sharp contrast, laminin‐1 did not induce capillary morphogen¬esis, and laminin‐1 did not induce activation of Src or Rho. Rather, laminin‐1 induced persistent activation of the GTPase Rac. Thus, these studies identify activation of Src and Rho as key mechanisms by which collagen I provokes capillary morphogenesis of microvascular endothelial cells, and they define marked differences between the functions of collagen I and laminin‐1 in regulating endothelial cell morphogenesis.—Liu, Y., Senger, D. R. Matrix‐specific activation of Src and Rho initiates capillary morphogenesis of endothelial cells.