Hipskind R A, Bilbe G
Institut de Genetique Moleculaire de Montpellier, CNRS, 1919 Route de Mende, 34293 Montpellier cedex 5, France.
Front Biosci. 1998 Aug 1;3:d804-16. 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.
环境信号引导成骨细胞增殖和分化。丝裂原活化蛋白（MAP）激酶通路在接收这些信号的膜结合受体与基因表达模式的变化之间提供了关键联系。哺乳动物细胞中的三种MAPK级联反应是：细胞外信号调节激酶（ERK）级联反应、应激激活蛋白激酶/c-jun氨基末端激酶（SAPK/JNK）级联反应和p38MAPK/RK/HOG级联反应。根据细胞类型和环境的不同，每种级联反应都有不同的作用，包括将应激、生长、分化和凋亡信号传递到细胞核。这些通路靶向一组重叠的转录因子，导致快速反应基因的差异激活，特别是原癌基因fos和jun家族的成员。这些蛋白质是转录因子AP-1的主要成分，AP-1在调节成骨细胞分化早期激活的基因中起核心作用。我们将详细讨论：a）这些通路的性质和激活；b）它们如何诱导c-fos表达；c）这些MAPK级联反应如何差异调节AP-1的活性，从而调节成骨细胞特异性基因表达。
