Mapkapk3, also known as mitogen-activated protein kinase-activated protein kinase 3, is a serine/threonine protein kinase. It is a key member of the p38 mitogen-activated protein kinase (MAPK) signaling pathway, which is activated by various stress stimuli. Mapkapk3 is involved in multiple cellular responses and gene regulation, playing a vital role in biological processes such as autophagy, stress response, and cell growth [1,2].

In a retinal disease study, a heterozygous c.518T>C (p.Leu173Pro) mutation in Mapkapk3 was identified in a family with Martinique crinkled retinal pigment epitheliopathy. Expression of the mutated allele in HEK cells led to mislocalization of the protein in the cytoplasm, cytoskeleton alteration, and cytodieresis inhibition. In Mapkapk3-/-mice, Bruch's membrane was irregular, indicating the role of Mapkapk3 in retinal physiology and Bruch's membrane/RPE pathophysiology [2]. Another study found that Mapkapk3 activates starvation-induced autophagy by phosphorylating Beclin 1 at serine 90, and this phosphorylation is blocked by BCL2 [1].

In conclusion, Mapkapk3 is crucial in the p38 MAPK signaling pathway, participating in various biological processes. Studies using gene knockout models, like the Mapkapk3-/-mice, have revealed its role in retinal diseases and autophagy, providing insights into disease mechanisms and potential therapeutic targets related to these areas [1,2].

References:

1. Wei, Yongjie, An, Zhenyi, Zou, Zhongju, Gaestel, Matthias, Levine, Beth. 2015. The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. In eLife, 4, . doi:10.7554/eLife.05289. https://pubmed.ncbi.nlm.nih.gov/25693418/

2. Meunier, Isabelle, Lenaers, Guy, Bocquet, Béatrice, Gaestel, Matthias, Hamel, Christian P. 2016. A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium. In Human molecular genetics, 25, 916-26. doi:10.1093/hmg/ddv624. https://pubmed.ncbi.nlm.nih.gov/26744326/