Glutamate‐Stimulated Activation of DNA Synthesis via Mitogen‐Activated Protein Kinase in Primary Astrocytes

• DOI: 10.1046/j.1471-4159.2000.0741931.x
• Publication Date: 2003-03-12T06:45:16Z
• Authors: Karin A. Schinkmann; Tae‐Aug Kim; Shalom Avraham
• Keywords: 0301 basic medicine; Glutamic Acid; DNA; Protein-Tyrosine Kinases; Receptors, Metabotropic Glutamate; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Pertussis Toxin; GTP-Binding Proteins; Astrocytes; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Animals; Calcium; Virulence Factors, Bordetella; Mitogen-Activated Protein Kinases; Phosphorylation; Protein Kinase C; Signal Transduction

Abstract: Glutamate is the major excitatory neurotransmitter in CNS. Although its role neurons has been studied extensively, little known about function astrocytes. We effects of glutamate on signaling pathways primary found that tyrosine kinase related adhesion focal (RAFTK) phosphorylated response to a time‐ and dose‐dependent manner. This phosphorylation was pertussis toxin (PTX) sensitive could be attenuated by depletion Ca 2+ from intracellular stores. RAFTK mediated primarily class I/II metabotropic receptors depends protein C (PKC) activation. treatment astrocytes also results significant increase activity mitogen‐activated kinases [extracellular signal‐related 1/2 (ERK1/2)]. Like phosphorylation, ERK1/2 activation PTX can PKC inhibition, suggesting might mediate glutamate‐dependent ERK1/2. Furthermore, we demonstrated stimulation leads DNA synthesis. Glutamate‐stimulated synthesis inhibited MAP inhibitor PD98059, astrocytes, signal via promote cell proliferation.