Hu E, Kim J B, Sarraf P, Spiegelman B M
Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Science. 1996 Dec 20;274(5295):2100-3. doi: 10.1126/science.274.5295.2100.
Adipocyte differentiation is an important component of obesity and other metabolic diseases. This process is strongly inhibited by many mitogens and oncogenes. Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and reduction of its transcriptional activity. Expression of PPARgamma with a nonphosphorylatable mutation at this site (serine-112) yielded cells with increased sensitivity to ligand-induced adipogenesis and resistance to inhibition of differentiation by mitogens. These results indicate that covalent modification of PPARgamma by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage.
脂肪细胞分化是肥胖症和其他代谢性疾病的一个重要组成部分。这一过程受到许多促有丝分裂原和癌基因的强烈抑制。几种抑制脂肪细胞分化的生长因子导致丝裂原活化蛋白（MAP）激酶介导的主要脂肪生成转录因子过氧化物酶体增殖物激活受体γ（PPARγ）磷酸化，并降低其转录活性。在该位点（丝氨酸-112）具有不可磷酸化突变的PPARγ表达产生了对配体诱导的脂肪生成敏感性增加且对促有丝分裂原抑制分化具有抗性的细胞。这些结果表明，血清和生长因子对PPARγ的共价修饰是脂肪细胞谱系中细胞生长与分化平衡的主要调节因子。
