MAP kinase signaling cascades and gene expression in osteoblasts

• Published in: Frontiers in bioscience Vol. 3; no. 4; pp. d804 - 816
• Main Authors: Hipskind, R A, Bilbe, G
• Format: Journal Article
• Language: English
• Published: United States Frontiers in Bioscience 1998
• Subjects: Animals; Biochemistry, Molecular Biology; Extracellular Signal-Regulated MAP Kinases - physiology; Gene Expression - physiology; Genes, fos - physiology; Humans; JNK Mitogen-Activated Protein Kinases - physiology; Life Sciences; MAP Kinase Signaling System - physiology; Osteoblasts - physiology; p38 Mitogen-Activated Protein Kinases - physiology; Promoter Regions, Genetic - physiology; Transcription Factor AP-1 - physiology; Animals Extracellular Signal-Regulated MAP Kinases/physiology Gene Expression/physiology Genes; fos/physiology Humans JNK Mitogen-Activated Protein Kinases/physiology MAP Kinase Signaling System/physiology Osteoblasts/physiology Promoter Regions (Genetics)/physiology Transcription Factor AP-1/physiology p38 Mitogen-Activated Protein Kinases/physiology
• ISSN: 1093-9946; 1093-4715
• DOI: 10.2741/A323

Environmental cues direct osteoblasts to proliferate and differentiate. The mitogen-activated protein (MAP) kinase pathways provide a key link between the membrane bound receptors that receive these cues and changes in the pattern of gene expression. The three MAPK cascades in mammalian cells are: the extracellular signal-regulated kinase (ERK) cascade, the stress activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) cascade and the p38MAPK/RK/HOG cascade. Each has varied roles, depending upon the cell type and context, that include transmitting stress, growth, differentiative and apoptotic signals to the nucleus. These pathways target an overlapping set of transcription factors that lead to the differential activation of rapid response genes, particularly members of the fos and jun family of proto-oncogenes. These proteins are the principal components of the transcription factor AP-1, which plays a central role in regulating genes activated early in osteoblast differentiation. We discuss in detail a) the nature and activation of these pathways b) how they induce c-fos expression and c) how these MAPK cascades can differentially regulate the activity of AP-1 and thereby osteoblast-specific gene expression.