Adhesion is required for protein kinase C-dependent activation of the Na+/H+ antiporter by platelet-derived growth factor.
Adhesion of normal, anchorage-dependent cells to a solid substratum leads to activation of the Na+/H+ antiporter and elevation of intracellular pH. These effects are mediated by extracellular matrix proteins, such as fibronectin, and their receptors, the integrins. Experiments using pharmacological inhibition and down-regulation of protein kinase C (PKC) in C3H 10T1/2 cells show that platelet-derived growth factor induces activation of the Na+/H+ antiporter by means of a PKC-dependent pathway in adherent cells but cannot do so in poorly adherent cells. Poorly adherent cells are, however, able to elevate intracellular pH in response to a phorbol ester, indicating that PKC and subsequent steps in the pathway are functional. These results indicate that coupling of platelet-derived growth factor to PKC activation requires cell adhesion.
Schwartz
M A
MA
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115.
Lechene
C
C
D000136:Acid-Base Equilibrium; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D051379:Mice; D009281:Naphthalenes; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002352:Carrier Proteins; D009281:Naphthalenes; D010982:Platelet-Derived Growth Factor; D011083:Polycyclic Compounds; D017923:Sodium-Hydrogen Exchangers; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate