Markou Thomais, Cieslak Danuta, Gaitanaki Catherine, Lazou Antigone
Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
Mol Cell Biochem. 2009 Feb;322(1-2):103-12. doi: 10.1007/s11010-008-9945-8. Epub 2008 Nov 11.
Gq-protein-coupled receptor (GqPCR) signalling is associated with the induction of cardiac myocyte hypertrophy, which is characterized by an increase in expression of immediate early genes via activation of pre-existing transcription factors. Here, we explore the role of MSK1 and MAPK signalling pathways in the regulation of the immediate early gene c-jun. The results provide further support for the role of MSK1 in cardiac myocyte hypertrophy and indicate that PE activates distinct signalling mechanisms which culminate with a complex activation of c-jun. ERK1/2 and JNKs are the principal kinases responsible for phosphorylation of c-Jun, whereas c-jun mRNA and protein up-regulation by PE is mediated by multiple signalling pathways that include MSK1, ERK1/2, p38-MAPK and JNKs. These signalling mechanisms seem to be critical to the phenotypic changes of cardiac myocytes in response to hypertrophic stimulation.
Gq蛋白偶联受体（GqPCR）信号传导与心肌细胞肥大的诱导有关，其特征是通过激活预先存在的转录因子使即刻早期基因的表达增加。在此，我们探讨了MSK1和丝裂原活化蛋白激酶（MAPK）信号通路在调控即刻早期基因c-jun中的作用。这些结果为MSK1在心肌细胞肥大中的作用提供了进一步支持，并表明去甲肾上腺素（PE）激活了不同的信号传导机制，最终导致c-jun的复杂激活。细胞外信号调节激酶1/2（ERK1/2）和应激活化蛋白激酶（JNKs）是负责c-Jun磷酸化的主要激酶，而PE对c-jun mRNA和蛋白质的上调是由包括MSK1、ERK1/2、p38丝裂原活化蛋白激酶（p38-MAPK）和JNKs在内的多种信号通路介导的。这些信号传导机制似乎对心肌细胞响应肥大刺激的表型变化至关重要。
