Src Family Kinases Csk and Actin Remodeling

Src-family kinases are essential for cell proliferation, differentiation, and adhesion [96]. However, uncontrolled Src-family kinase activity leads to constitutive activation of mitogenic pathways, tumor promotion, and loss of cell attachment. Therefore, tight regulation of Src-family kinase activity is essential. The requirement for tight control of Src-family kinase activity is readily apparent in the regulation of actin/cell surface/extracellular matrix adhesions [97-100]. Both Src and Fyn are translocated to newly forming focal contacts during cell spreading. Src-family kinase activity is essential for the maintenance of these structures: inhibition of Src-family kinase activity leads to disassembly of adhesions. Paradoxically, constitutively active forms of Src also disrupt cell adhesion, and therefore the activity of Src in focal adhesions must be carefully regulated. During cell spreading there is an initial disruption of plasma membrane-actin attachments to allow membrane extension at the leading edge of the cell, followed by assembly of focal contacts and actin filaments behind the leading edge. Src-family kinases are activated at the cell edge during the initial stage of cell spreading to transiently relieve actin-induced tension at the plasma membrane, but must then be attenuated to allow actin reassembly. Attenuation occurs through phosphorylation by Csk. Csk-deficient cells exhibit unregulated Src-family kinase activity, hyperphosphorylation of actin-associated substrate proteins, impaired stress fiber formation and defects in cell adhesion [97]. Interestingly, anti-sense-mediated suppression of caveolin expression results in similar phenotypes, including elevated Src-family kinase activity and loss of cell adhesion [7,101].

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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