Calmodulin-mediated regulation of the epidermal growth factor receptor.
In this review, we first describe the mechanisms by which the epidermal growth factor receptor generates a Ca(2+) signal and, subsequently, we compile the available experimental evidence regarding the role that the Ca(2+)/calmodulin complex, formed after the rise in cytosolic free Ca(2+) concentration, exerts on the receptor. We focus not only on the indirect action that Ca(2+)/calmodulin exerts on the epidermal growth factor receptor, as a result of the activation of distinct calmodulin-dependent kinases, but also, and more extensively, on the direct interaction of Ca(2+)/calmodulin with the receptor. We also describe several mechanistic models that could account for the Ca(2+)/calmodulin-mediated regulation of epidermal growth factor receptor activity. The control exerted by calmodulin on distinct epidermal growth factor receptor-mediated cellular functions is also discussed. Finally, the phosphorylation of this Ca(2+) sensor by the epidermal growth factor receptor is highlighted.
Sánchez-González
Pablo
P
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Jellali
Karim
K
Villalobo
Antonio
A
D000818:Animals; D001665:Binding Sites; D020013:Calcium Signaling / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002147:Calmodulin / Q000737:chemistry / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D066246:ErbB Receptors / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000502:physiology; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D055672:Static Electricity
D002147:Calmodulin; D043562:Receptors, G-Protein-Coupled; D066246:ErbB Receptors; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases