Brain Res Mol Brain Res 2003,
PMID: 14597235
Baldassa, Simona; Zippel, Renata; Sturani, Emmapaola
In neurons, membrane depolarization triggers pleiotropic signaling which includes the activation of the small GTPases, Ras and Rap1, and the mitogen-activated protein kinases (MAPKs) Erk1/2. We have studied the intracellular signaling mechanisms which regulate these events in mouse-cultured cortical neurons. We show that depolarization induces activation of both Ras and Rap1, although with different kinetics: Ras activation is strong and fast while Rap1 activation is slower and weaker. Blockade of calmodulin affects the GTP-loading of Ras and Rap1 and prevents the MAPK response. Moreover, protein kinase A (PKA) activity is required for depolarization-induced Rap1 activation and full Erk stimulation, but is not involved in that of Ras. This PKA-dependent Rap1 activation does not require Src family kinases, but, in contrast to Ras, is sensitive to genistein, indicating the involvement of a tyrosine kinase-dependent mechanism. Our data provide new insights into the regulation of Ras and Rap1 activation in neurons.
Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
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Text Mining Data
Rap1 → protein kinase A (PKA): "
Moreover,
protein kinase A (PKA) activity is
required for depolarization induced
Rap1 activation and full Erk stimulation, but is not involved in that of Ras
"
Erk → protein kinase A (PKA): "
Moreover, protein kinase A (PKA) activity is required for depolarization induced Rap1 activation and full Erk stimulation, but is not involved in that of Ras
"
Rap1 → PKA: "
This PKA dependent Rap1 activation does not require Src family kinases, but, in contrast to Ras, is sensitive to genistein, indicating the involvement of a tyrosine kinase dependent mechanism
"
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