Requirement of Caveolae Microdomains in Extracellular Signal-Regulated Kinase and Focal Adhesion Kinase Activation Induced by Endothelin-1 in Primary Astrocytes

We investigated the influence of stretch and contractile activity on load-induced activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK)1/2 in isolated rat hearts. Increases of diastolic pressure from ∼0 to ∼15 mmHg rapidly increased FAK tyrosine phosphorylation (maximum: 2.3-fold) and binding to c-Src (maximum: 2.8-fold) and Grb2 (maximum: 3.6-fold). This was paralleled by activation (maximum: 2.8-fold) and binding of ERK1/2 to FAK. FAK and ERK1/2 were immunolocalized at sarcolemmal sites of cardiac myocytes and in the nuclei, in the case of ERK1/2. Balloon inflation to raise ventricular pressure in hearts perfused with cardioplegic solution also activated FAK and ERK1/2. However, increases in contractile activity induced by increasing calcium concentration in the perfusate (from 0.5 to 5 mM) did not activate the FAK multicomponent signaling complex or ERK1/2 in the myocardium. These results indicate that stretch rather than contractile activity induces FAK and ERK1/2 activation in the myocardium. In addition, the activation and binding of ERK1/2 to FAK suggest that FAK drives the load-induced activation of ERK1/2.

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Quantitative Relationship among Integrin-Ligand Binding, Adhesion, and Signaling via Focal Adhesion Kinase and Extracellular Signal-regulated Kinase 2

Journal of Biological Chemistry ◽

10.1074/jbc.274.38.27119 ◽

1999 ◽

Vol 274 (38) ◽

pp. 27119-27127 ◽

Cited By ~ 72

Author(s):

Anand R. Asthagiri ◽

Celeste M. Nelson ◽

Alan F. Horwitz ◽

Douglas A. Lauffenburger

Keyword(s):

Ligand Binding ◽

Focal Adhesion Kinase ◽

Focal Adhesion ◽

Quantitative Relationship ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Integrin Ligand

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Differential Requirement of Gα12, Gα13, Gαq, and Gβγ for Endothelin-1-Induced c-Jun NH2-Terminal Kinase and Extracellular Signal-Regulated Kinase Activation

Molecular Pharmacology ◽

10.1124/mol.63.3.478 ◽

2003 ◽

Vol 63 (3) ◽

pp. 478-488 ◽

Cited By ~ 66

Author(s):

Ken Arai ◽

Yoshiko Maruyama ◽

Motohiro Nishida ◽

Shihori Tanabe ◽

Shuichi Takagahara ◽

...

Keyword(s):

Kinase Activation ◽

Extracellular Signal Regulated Kinase ◽

Endothelin 1 ◽

Extracellular Signal

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Neogenin Regulates Skeletal Myofiber Size and Focal Adhesion Kinase and Extracellular Signal-regulated Kinase Activities In Vivo and In Vitro

Molecular Biology of the Cell ◽

10.1091/mbc.e09-06-0491 ◽

2009 ◽

Vol 20 (23) ◽

pp. 4920-4931 ◽

Cited By ~ 49

Author(s):

Gyu-Un Bae ◽

Youn-Joo Yang ◽

Guoying Jiang ◽

Mingi Hong ◽

Hye-Jin Lee ◽

...

Keyword(s):

Focal Adhesion Kinase ◽

Focal Adhesion ◽

Myogenic Differentiation ◽

Dependent Manner ◽

Extracellular Signal Regulated Kinase ◽

Myotube Formation ◽

Extracellular Signal ◽

Repulsive Guidance Molecule

A variety of signaling pathways participate in the development of skeletal muscle, but the extracellular cues that regulate such pathways in myofiber formation are not well understood. Neogenin is a receptor for ligands of the netrin and repulsive guidance molecule (RGM) families involved in axon guidance. We reported previously that neogenin promoted myotube formation by C2C12 myoblasts in vitro and that the related protein Cdo (also Cdon) was a potential neogenin coreceptor in myoblasts. We report here that mice homozygous for a gene-trap mutation in the Neo1 locus (encoding neogenin) develop myotomes normally but have small myofibers at embryonic day 18.5 and at 3 wk of age. Similarly, cultured myoblasts derived from such animals form smaller myotubes with fewer nuclei than myoblasts from control animals. These in vivo and in vitro defects are associated with low levels of the activated forms of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), both known to be involved in myotube formation, and inefficient expression of certain muscle-specific proteins. Recombinant netrin-2 activates FAK and ERK in cultured myoblasts in a neogenin- and Cdo-dependent manner, whereas recombinant RGMc displays lesser ability to activate these kinases. Together, netrin-neogenin signaling is an important extracellular cue in regulation of myogenic differentiation and myofiber size.

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