scholarly journals Integrin Activation and Focal Complex Formation in Cardiac Hypertrophy

2000 ◽  
Vol 275 (45) ◽  
pp. 35624-35630 ◽  
Author(s):  
Martin Laser ◽  
Christopher D. Willey ◽  
Wenjing Jiang ◽  
George Cooper ◽  
Donald R. Menick ◽  
...  
Keyword(s):  
Complex Formation ◽  
Cardiac Hypertrophy ◽  
Integrin Activation ◽  
Focal Complex

scholarly journals The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases.

1995 ◽  
Vol 131 (6) ◽  
pp. 1857-1865 ◽  
Author(s):  
N A Hotchin ◽  
A Hall
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Complex Formation ◽  
Map Kinase ◽  
Human Fibroblasts ◽  
Focal Adhesions ◽  
Small Gtpases ◽  
Wide Range ◽  
Focal Complex ◽  
Rho Family

Interaction of cells with extracellular matrix via integrin adhesion receptors plays an important role in a wide range of cellular: functions, for example cell growth, movement, and differentiation. Upon interaction with substrate, integrins cluster and associate with a variety of cytoplasmic proteins to form focal complexes and with the actin cytoskeleton. Although the intracellular signals induced by integrins are at present undefined, it is thought that they are mediated by proteins recruited to the focal complexes. It has been suggested, for example, that after recruitment to focal adhesions p125FAK can activate the ERK1/2 MAP kinase cascade. We have previously reported that members of the rho family of small GTPases can trigger the assembly of focal complexes when activated in cells. Using microinjection techniques, we have now examined the role of the extracellular matrix and of the two GTP-binding proteins, rac and rho, in the assembly of integrin complexes in both mouse and human fibroblasts. We find that the interaction of integrins with extracellular matrix alone is not sufficient to induce integrin clustering and focal complex formation. Similarly, activation of rho or rac by extracellular growth factors does not lead to focal complex formation in the absence of matrix. Focal complexes are only assembled in the presence of both matrix and functionally active members of the rho family. In agreement with this, the interaction of integrins with matrix in the absence of rho/rac activity is unable to activate the ERK1/2 kinases in Swiss 3T3 cells. In fact, ERK1/2 can be activated fully by growth factors in the absence of matrix and it seems unlikely, therefore, that the adhesion dependence of fibroblast growth is mediated through the ras/MAP kinase pathway. We conclude that extracellular matrix is not sufficient to trigger focal complex assembly and subsequent integrin-dependent signal transduction in the absence of functionally active members of the rho family of GTPases.

TGFβ-induced focal complex formation in epithelial cells is mediated by activated ERK and JNK MAP kinases and is independent of Smad4

2005 ◽  
Vol 386 (3) ◽  
Author(s):  
Yukiko Imamichi ◽  
Oliver Waidmann ◽  
Ramona Hein ◽  
Pinelopi Eleftheriou ◽  
Klaudia Giehl ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Complex Formation ◽  
Map Kinases ◽  
Focal Complex

MEGAP impedes cell migration via regulating actin and microtubule dynamics and focal complex formation

2006 ◽  
Vol 312 (12) ◽  
pp. 2379-2393 ◽  
Author(s):  
Ying Yang ◽  
Marco Marcello ◽  
Volker Endris ◽  
Rainer Saffrich ◽  
Roger Fischer ◽  
...  
Keyword(s):  
Cell Migration ◽  
Complex Formation ◽  
Microtubule Dynamics ◽  
Focal Complex

scholarly journals Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases

2010 ◽  
Vol 190 (4) ◽  
pp. 663-674 ◽  
Author(s):  
Chan-Soo Lee ◽  
Chang-Ki Choi ◽  
Eun-Young Shin ◽  
Martin Alexander Schwartz ◽  
Eung-Gook Kim
Keyword(s):  
Complex Formation ◽  
Atpase Activity ◽  
Myosin Ii ◽  
Guanine Nucleotide Exchange Factors ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors ◽  
Cell Protrusion ◽  
Focal Complex

Cell migration requires the coordinated spatiotemporal regulation of actomyosin contraction and cell protrusion/adhesion. Nonmuscle myosin II (MII) controls Rac1 and Cdc42 activation, and cell protrusion and focal complex formation in migrating cells. However, these mechanisms are poorly understood. Here, we show that MII interacts specifically with multiple Dbl family guanine nucleotide exchange factors (GEFs). Binding is mediated by the conserved tandem Dbl homology–pleckstrin homology module, the catalytic site of these GEFs, with dissociation constants of ∼0.3 µM. Binding to the GEFs required assembly of the MII into filaments and actin-stimulated ATPase activity. Binding of MII suppressed GEF activity. Accordingly, inhibition of MII ATPase activity caused release of GEFs and activation of Rho GTPases. Depletion of βPIX GEF in migrating NIH3T3 fibroblasts suppressed lamellipodial protrusions and focal complex formation induced by MII inhibition. The results elucidate a functional link between MII and Rac1/Cdc42 GTPases, which may regulate protrusion/adhesion dynamics in migrating cells.

scholarly journals ARF6 Is Required for Growth Factor- and Rac-Mediated Membrane Ruffling in Macrophages at a Stage Distal to Rac Membrane Targeting

1999 ◽  
Vol 19 (12) ◽  
pp. 8158-8168 ◽  
Author(s):  
Qing Zhang ◽  
Jero Calafat ◽  
Hans Janssen ◽  
Steven Greenberg
Keyword(s):  
Plasma Membrane ◽  
Growth Factor ◽  
Complex Formation ◽  
Functional Responses ◽  
Membrane Ruffling ◽  
Focal Complex ◽  
Direct Targeting ◽  
Guanine Nucleotide Binding ◽  
Effector Pathways ◽  
Cytoskeletal Responses

ABSTRACT Activation of Rac1, a member of the Rho family of GTPases, is associated with multiple cellular responses, including membrane ruffling and focal complex formation. The mechanisms by which Rac1 is coupled to these functional responses are not well understood. It was recently shown that ARF6, a GTPase implicated in cytoskeletal alterations and a membrane recycling pathway, is required for Rac1-dependent phagocytosis in macrophages (Q. Zhang et al., J. Biol. Chem. 273:19977–19981, 1998). To determine whether ARF6 is required for Rac1-dependent cytoskeletal responses in macrophages, we expressed wild-type (WT) or guanine nucleotide binding-deficient alleles (T27N) of ARF6 in macrophages coexpressing activated alleles of Rac1 (Q61L) or Cdc42 (Q61L) or stimulated with colony-stimulating factor 1 (CSF-1). Expression of ARF6 T27N but not ARF6 WT inhibited ruffles mediated by Rac1 Q61L or CSF-1. In contrast, expression of ARF6 T27N did not inhibit Rac1 Q61L-mediated focal complex formation and did not impair Cdc42 Q61L-mediated filopodial formation. Cryoimmunogold electron microscopy demonstrated the presence of ARF6 in membrane ruffles induced by either CSF-1 or Rac1 Q61L. Addition of CSF-1 to macrophages led to the redistribution of ARF6 from the interior of the cell to the plasma membrane, suggesting that this growth factor triggers ARF6 activation. Direct targeting of Rac1 to the plasma membrane did not bypass the blockade in ruffling induced by ARF6 T27N, indicating that ARF6 regulates a pathway leading to membrane ruffling that occurs after the activation and membrane association of Rac. These data demonstrate that intact ARF6 function is required for coupling activated Rac to one of several effector pathways and suggest that a principal function of ARF6 is to coordinate Rac activation with plasma membrane-based protrusive events.

scholarly journals The relationship between force and focal complex development

2002 ◽  
Vol 159 (4) ◽  
pp. 695-705 ◽  
Author(s):  
Catherine G. Galbraith ◽  
Kenneth M. Yamada ◽  
Michael P. Sheetz
Keyword(s):  
Extracellular Matrix ◽  
Complex Formation ◽  
Focal Adhesions ◽  
Mechanical Force ◽  
Force Transmission ◽  
Integrin Receptors ◽  
Focal Complex ◽  
Complex Development ◽  
The Relationship

To adhere and migrate, cells must be capable of applying cytoskeletal force to the extracellular matrix (ECM) through integrin receptors. However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether engagement of force transmission requires maturation of the adhesion. Here, we show that initial integrin–ECM adhesions become capable of exerting migration force with the recruitment of vinculin, a marker for focal complexes, which are precursors of focal adhesions. We are able to induce the development of focal complexes by the application of mechanical force to fibronectin receptors from inside or outside the cell, and we are able to extend focal complex formation to vitronectin receptors by the removal of c-Src. These results indicate that cells use mechanical force as a signal to strengthen initial integrin–ECM adhesions into focal complexes and regulate the amount of migration force applied to individual adhesions at localized regions of the advancing lamella.

scholarly journals Necl-5/Poliovirus Receptor Interacts inciswith Integrin αVβ3and Regulates Its Clustering and Focal Complex Formation

2007 ◽  
Vol 282 (25) ◽  
pp. 18481-18496 ◽  
Author(s):  
Yukiko Minami ◽  
Wataru Ikeda ◽  
Mihoko Kajita ◽  
Tsutomu Fujito ◽  
Hisayuki Amano ◽  
...  
Keyword(s):  
Complex Formation ◽  
Poliovirus Receptor ◽  
Focal Complex

421 The NFATc2 isoform plays a major role in calcineurin-induced cardiac hypertrophy

2006 ◽  
Vol 5 (1) ◽  
pp. 98-98
Author(s):  
M BOURAJJAJ ◽  
A ARMAND ◽  
B WEIJTS ◽  
L DEWINDT
Keyword(s):  
Cardiac Hypertrophy
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