MacKenzie S J, Yarwood S J, Peden A H, Bolger G B, Vernon R G, Houslay M D
Division of Biochemistry, Davidson and Wolfson Buildings, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom.
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3549-54. doi: 10.1073/pnas.95.7.3549.
The challenge of 3T3-F442A fibroblasts with growth hormone led to both a decrease in the mobility on SDS/PAGE and activation of the PDE4A cyclic AMP-specific phosphodiesterase isoform PDE4A5. Activation was mediated by a JAK-2-dependent pathway coupled to the activation of phosphatidylinositol 3-kinase and p70S6 kinase. Activation was not dependent on the ability of growth hormone to stimulate ERK2 or protein kinase C or any effect on transcription. Blockade of activation of murine PDE4A5 ablated the ability of growth hormone to decrease intracellular cAMP levels. Antisense depletion of murine PDE4A5 mimicked the ability of rolipram to enhance the growth hormone-stimulated differentiation of 3T3-F442A cells to adipocytes. It is suggested that activation of PDE4A5 by growth hormone serves as a brake on the differentiation processes.
用生长激素刺激3T3 - F442A成纤维细胞，导致其在SDS/PAGE上的迁移率降低，并激活了环磷酸腺苷特异性磷酸二酯酶同工型PDE4A5。这种激活是由一条依赖JAK - 2的信号通路介导的，该通路与磷脂酰肌醇3激酶和p70S6激酶的激活相关联。激活并不依赖于生长激素刺激ERK2或蛋白激酶C的能力，也不依赖于其对转录的任何影响。对小鼠PDE4A5激活的阻断消除了生长激素降低细胞内cAMP水平的能力。小鼠PDE4A5的反义缺失模拟了咯利普兰增强生长激素刺激3T3 - F442A细胞向脂肪细胞分化的能力。提示生长激素对PDE4A5的激活起到了抑制分化过程的作用。
