Chen Lin, Zhang J Jillian, Huang Xin-Yun
Department of Physiology, Cornell University Weill Medical College, New York, New York 10021, USA.
J Biol Chem. 2008 May 16;283(20):13799-805. doi: 10.1074/jbc.M800555200. Epub 2008 Mar 19.
Cell migration is critical for animal development and physiological as well as pathological responses. One important step during cell migration is the formation of lamellipodia at the leading edge of migrating cells. Here we report that the second messenger cAMP inhibits the migration of mouse embryonic fibroblast cells and mouse breast tumor cells. cAMP acts downstream of the small GTPase Rac and interferes with the formation of lamellipodia. Moreover, cAMP decreases the phosphorylation of the myosin light chain at the leading edge of cells and increases the phosphorylation of the vasodilator-stimulated phosphoprotein. Together with our previous report of a positive role of another second messenger, cGMP, in lamellipodium formation, our data indicate that cAMP and cGMP play opposite roles in modulating lamellipodium formation.
细胞迁移对于动物发育、生理反应以及病理反应至关重要。细胞迁移过程中的一个重要步骤是在迁移细胞的前沿形成片状伪足。在此我们报告,第二信使环磷酸腺苷(cAMP)抑制小鼠胚胎成纤维细胞和小鼠乳腺肿瘤细胞的迁移。cAMP在小GTP酶Rac的下游起作用,并干扰片状伪足的形成。此外,cAMP降低细胞前沿肌球蛋白轻链的磷酸化水平,并增加血管舒张刺激磷蛋白的磷酸化水平。结合我们之前关于另一种第二信使环磷酸鸟苷(cGMP)在片状伪足形成中起积极作用的报告,我们的数据表明cAMP和cGMP在调节片状伪足形成中发挥相反的作用。