Cell Receptors as Mediators of Metabolic Signals

Abstract

During the last 5 years, substantial progress has been made in understanding the pathways that regulate the cell response to extrinsic signaling molecules including growth factors, ions, and pharmacologic agents. Many of the responses are linked through enzymatic activation, particularly phosphorylation reactions, and these may result in intracellular ion changes and transcriptional activation of a limited number of genes. A central molecule in a number of response pathways is protein kinase C, a family of enzymes that adds phosphate groups to serine and threonine residues on specific target proteins. Protein kinase C is an important regulator of epidermal differentiation and has a high affinity for certain toxicants that bind to the enzyme and activate its phosphorylating activity. Protein kinase C activation is linked to several dermatologic disorders including contact dermatitis, psoriasis, and neoplasia. Natural inhibitors of the enzyme have been identified, and these, or their derivatives, may provide powerful new pharmacologic agents for dermatologic therapeutics.