Intracellular Signaling Mechanisms of Epidermal Keratinocytes

Abstract

Recent findings abont the intracellular signaling mechanisms of epidermal keratinocytes are described in this report. Epidermal keratinocytes undergo differentiation as they leave the basement membrane and form the multilayered epidermis. Adhesion signals regulate early phase keratinocyte differentiation. These signals are transmitted to intracellular signaling cascades via integrins through integrin-linked kinase (ILK) in a phosphatidyl inosito (PI) 3 kinase-dependent manner, and PI3K regulates early phase keratinocyte differentiation. The mitogen activated protein (MAP) kinase cascade has been characterized as a core signal transduction pathway that is conserved from yeast to humans. This cascade consists of three distinct protein kinase families, MAP kinase, MAP kinase kinase (MAPKK), and MAP kinase kinase kinase (MAPKKK). MAPKKK activates MAPKK, which in turn activates MAP kinase. The MAP kinase superfamily consists of the classical MAP kinase (extracellular signal regulating kinase; ERK) family, the c-Jun N-terminal kinase (JNK, also known as stress-activated protein kinase; SAPK) family, and the p38 MAP kinase family. The cascade plays an essential role in diverse intracellular signaling processes, including cell growth, cell cycle regulation, differentiation, and apoptosis. Apoptosis signal regulating kinase-1 (ASK1) is a MAP kinase kinase kinase that activates the p38 MAP kinase cascade. During epidermal differentiation, ASK1 is expressed in the upper epidermis and regulates the late phase of keratinocyte differentiation.