Straussman R, Even L, Ravid S
Department of Biochemistry, Hadassah Medical School The Hebrew University, Jerusalem, Israel.
J Cell Sci. 2001 Aug;114(Pt 16):3047-57. doi: 10.1242/jcs.114.16.3047.
To explore the involvement and regulation of the nonmuscle myosin II heavy chains isoforms, MHC-A and MHC-B in the chemotaxis of metastatic tumor cells, we analyzed the changes in phosphorylation and cellular localization of these isoforms upon stimulation of prostate tumor cells with epidermal growth factor (EGF). EGF stimulation of prostate tumor cells resulted in transient increases in MHC-A and MHC-B phosphorylation and subcellular localization with quite different kinetics. Furthermore, the kinetics of subcellular localization correlated with the in vivo kinetics of MHC-B phosphorylation but not of MHC-A phosphorylation, suggesting different modes of regulation for these myosin II isoforms. We further showed that protein kinase C (PKC) is involved in the EGF-dependent phosphorylation of MHC-A and MHC-B. To our knowledge, this is the first report demonstrating that MHC phosphorylation might regulate its subcellular localization and that the EGF signal is transmitted to MHC-A and MHC-B via PKC. The correlation between MHC-B phosphorylation and localization in response to EGF stimulation might suggest that MHC-B is the myosin II isoform that is involved in chemotaxis.
为了探究非肌肉肌球蛋白II重链亚型MHC-A和MHC-B在转移性肿瘤细胞趋化作用中的参与情况及调控机制，我们分析了用表皮生长因子（EGF）刺激前列腺肿瘤细胞后，这些亚型的磷酸化和细胞定位变化。EGF刺激前列腺肿瘤细胞导致MHC-A和MHC-B的磷酸化及亚细胞定位出现短暂增加，且动力学差异显著。此外，亚细胞定位的动力学与MHC-B磷酸化的体内动力学相关，但与MHC-A磷酸化的体内动力学无关，这表明这些肌球蛋白II亚型存在不同的调控模式。我们进一步表明蛋白激酶C（PKC）参与了MHC-A和MHC-B的EGF依赖性磷酸化。据我们所知，这是首次报道表明MHC磷酸化可能调控其亚细胞定位，且EGF信号通过PKC传递至MHC-A和MHC-B。EGF刺激后MHC-B磷酸化与定位之间的相关性可能表明MHC-B是参与趋化作用的肌球蛋白II亚型。
