MAP kinase cascades regulate cold response by modulating ICE1 protein stability

Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. Our study shows that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates cold response. MPK3 and MPK6 can phosphorylate ICE1, a bHLH transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities, and has a positive role in cold response. In addition, the MAPKKK YDA, and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold-activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response.

丝裂原活化蛋白激酶（Mitogen-activated protein kinase, MAPK）级联通路是一类重要的信号模块，可将环境刺激转化为细胞应答。本研究发现，促分裂原活化蛋白激酶3（MPK3）、促分裂原活化蛋白激酶4（MPK4）和促分裂原活化蛋白激酶6（MPK6）在低温处理后迅速被激活。mpk3和mpk6突变体的CBF基因表达量上调，且耐寒性增强；而植物中促分裂原活化蛋白激酶激酶4/5（MKK4/5）-促分裂原活化蛋白激酶3/6（MPK3/6）级联通路的组成型激活则会导致CBF基因表达量下调，且对低温胁迫更为敏感，这表明MKK4/5-MPK3/6级联通路负调控植物低温应答。促分裂原活化蛋白激酶3（MPK3）和促分裂原活化蛋白激酶6（MPK6）能够磷酸化调控CBF基因表达的碱性螺旋-环-螺旋转录因子ICE1，且该磷酸化修饰会促进ICE1的降解。值得注意的是，促分裂原活化蛋白激酶激酶激酶1（MEKK1）-促分裂原活化蛋白激酶激酶2（MKK2）-促分裂原活化蛋白激酶4（MPK4）通路可组成型抑制MPK3和MPK6的活性，并在植物低温应答中发挥正向调控作用。此外，促分裂原活化蛋白激酶激酶激酶（MAPKKK）家族成员YDA以及两种钙/钙调素调控类受体激酶CRLK1和CRLK2，可负调控MPK3/6的低温激活过程。本研究结果揭示了MAPK级联通路在植物低温应答调控中的重要功能。