CYCLIC AMP-DEPENDENT PROTEIN-KINASE INHIBITS THE ACTIVITY OF MYOGENIC HELIX-LOOP-HELIX PROTEINS
CYCLIC AMP-DEPENDENT PROTEIN-KINASE INHIBITS THE ACTIVITY OF MYOGENIC HELIX-LOOP-HELIX PROTEINS
复制标题
DOI：
10.1128/mcb.12.10.4478
复制
发表时间：
1992-10-01
影响因子：
5.3
通讯作者：
OLSON, EN
中科院分区：
文献类型：
--
作者：
LI, L;HELLERHARRISON, R;OLSON, EN
骨骼肌细胞的分化受到环腺苷酸（cAMP）信号转导途径的抑制。在这里，我们报告说，cAMP依赖性蛋白激酶（PKA）的催化亚基可以取代cAMP和抑制肌肉特异性转录沉默MyoD家族的调节因子，其中包括MyoD，肌细胞生成素，myf5和MRF4的活性。PKA催化（C）亚基的抑制作用针对共有序列CANNTG，CANNTG是这些肌原性调节因子的DNA结合和转录激活的靶点。在体外和体内肌生成素的磷酸肽映射显示两个PKA磷酸化位点，都在碱性区域内。然而，PKA对肌细胞生成素功能的抑制不需要这些位点的直接磷酸化，而是涉及一个或多个中间步骤的间接机制。通过调节cAMP信号通路调节MyoD家族的转录活性可能是某些肽生长因子对肌肉特异性基因表达的抑制作用的原因，也可能决定不同细胞类型对这些肌源性调节剂的肌源性转化的反应。
Differentiation of skeletal muscle cells is inhibited by the cyclic AMP (cAMP) signal transduction pathway. Here we report that the catalytic subunit of cAMP-dependent protein kinase (PKA) can substitute for cAMP and suppress muscle-specific transcription by silencing the activity of the MyoD family of regulatory factors, which includes MyoD, myogenin, myf5, and MRF4. Repression by the PKA catalytic (C) subunit is directed at the consensus sequence CANNTG, the target for DNA binding and transcriptional activation by these myogenic regulators. Phosphopeptide mapping of myogenin in vitro and in vivo revealed two PKA phosphorylation sites, both within the basic region. However, repression of myogenin function by PKA does not require direct phosphorylation of these sites but instead involves an indirect mechanism with one or more intermediate steps. Regulation of the transcriptional activity of the MyoD family by modulation of the cAMP signaling pathway may account for the inhibitory effects of certain peptide growth factors on muscle-specific gene expression and may also determine the responsiveness of different cell types to myogenic conversion by these myogenic regulators.