Distinct Mechanisms Mediate the Initial and Sustained Phases of Integrin-mediated Activation of the Raf/MEK/Mitogen-activated Protein Kinase Cascade (original) (raw)

1998, Journal of Biological Chemistry

Cell-Extracellular Matrix Interactions Stimulate the AP-1 Transcription Factor in an Integrin-Linked Kinase- and Glycogen Synthase Kinase 3-Dependent Manner

Molecular and Cellular Biology, 1999

Integrin-mediated interactions of cells with components of the extracellular matrix regulate cell survival, cell proliferation, cell differentiation, and cell migration. Some of these physiological responses are regulated via activation of transcription factors such as activator protein 1 (AP-1). Integrin-linked kinase (ILK) is an ankyrin repeat containing serine-threonine protein kinase whose activity is rapidly and transiently stimulated by cell-fibronectin interactions as well as by insulin stimulation. ILK activates protein kinase B and inhibits the glycogen synthase kinase 3 (GSK-3) activity in a phosphatidylinositol-3-kinase (PI 3-kinase)-dependent manner. We now show that cell adhesion to fibronectin results in a rapid and transient stimulation of AP-1 activity. At the same time, the kinase activity of ILK is stimulated whereas that of GSK-3 is inhibited. This fibronectin-dependent activation of AP-1 activity is inhibited in a dose-dependent manner if the cells are transfecte...

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

1995

Abstract 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.

Loading...

Loading Preview

Sorry, preview is currently unavailable. You can download the paper by clicking the button above.