Identification of a mitogen-activated protein kinase kinase (AccMKK4) from Apis cerana cerana and its involvement in various stress responses.

The mitogen-activated protein kinase (MAPK) cascade pathway is a ubiquitous signal transduction pathway in eukaryotes that regulates a variety of immune responses. This study accomplished the first isolation of an AccMKK4 gene from Apis cerana cerana and explored its function. Yeast two-hybrid experiments proved that AccMKK4 can interact with Accp38b, and the silencing of AccMKK4 in honeybees downregulated the expression level of Accp38b, which suggests that AccMKK4 might participate in the oxidative stress response through the p38 MAPK pathway. Tissue-specific expression levels of AccMKK4 analysis showed that AccMKK4 in the thorax, particularly muscle tissue, was higher than that in other tissues. The qRT-PCR results from different conditions demonstrated that AccMKK4 responds to various environmental stresses. After AccMKK4 silencing, the transcription level of some antioxidant genes and the activity of antioxidant-related enzymes are reduced, which indicated that AccMKK4 plays an important role in resistance against oxidative stress caused by external stimuli. In summary, our findings indicate that AccMKK4 probably plays an indispensable role in the response of honeybees to environmental stress and might aid for further research on the role of the MAPK cascade pathway in the antioxidant defence mechanisms of insects.