Stimulation of growth factor receptor signal transduction by activation of voltage-sensitive calcium channels.
To understand the mechanisms by which electrical activity may generate long-term responses in the nervous system, we examined how activation of voltage-sensitive calcium channels (VSCCs) can stimulate the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Calcium influx through L-type VSCCs leads to tyrosine phosphorylation of the adaptor protein Shc and its association with the adaptor protein Grb2, which is bound to the guanine nucleotide exchange factor Sos1. In response to calcium influx, Shc, Grb2, and Sos1 inducibly associate with a 180-kDa tyrosine-phosphorylated protein, which was determined to be the epidermal growth factor receptor (EGFR). Calcium influx induces tyrosine phosphorylation of the EGFR to levels that can activate the MAPK signaling pathway. Thus, ion channel activation stimulates growth factor receptor signal transduction.
Rosen
L B
LB
Department of Neurology, Children's Hospital, Boston, MA 02115, USA.
Greenberg
M E
ME
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D008954:Models, Biological; D016716:PC12 Cells; D010766:Phosphorylation; D019000:Phosphotyrosine; D011189:Potassium Chloride / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism; D020837:SOS1 Protein; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000187:drug effects; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015220:Calcium Channels; D005656:Fungal Proteins; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D011506:Proteins; D012097:Repressor Proteins; D020837:SOS1 Protein; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D011189:Potassium Chloride; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium