iProXProteomicsXiaoshuai ZhangPeriplaneta Americanahttp://www.iprox.org/page/project.html?id=IPX000771900020210029@m.scnu.edu.cnInstitute of Insect Science and Technology &amp; School of Life Sciences, South China Normal UniversityiProXAppendage regeneration relies on the formation of blastema, a heterogeneous cellular structure formed at the injury site. However, little is known about the early injury-activated signaling pathways that trigger blastema formation during appendage regeneration. Here, we provide compelling evidence that the extracellular signal-regulated kinase (ERK)-activated casein kinase 2 (CK-2), which has not been previously implicated in appendage regeneration, triggers blastema formation during leg regeneration in the American cockroach, <i>Periplaneta americana</i>. After amputation, CK-2 undergoes rapid activation through ERK-induced phosphorylation within blastema cells. RNAi knockdown of <i>CK-2</i> severely impairs blastema formation by repressing cell proliferation through down-regulating mitosis-related genes. Evolutionarily, the regenerative role of CK-2 is conserved in zebrafish caudal fin regeneration via promoting blastema cell proliferation. Together, we find and demonstrate that the ERK-activated CK-2 triggers blastema formation in both cockroach and zebrafish, helping explore initiation factors during appendage regeneration.ERK-activated CK-2 triggers blastema formation during appendage regeneration.Zhang Xiao-Shuai XS, Wei Lin L, Zhang Wei W, Zhang Fei-Xue FX, Li Lin L, Li Liang L, Wen Yejie Y, Zhang Jia-Hui JH, Liu Suning S, Yuan Dongwei D, Liu Yanmei Y, Ren Chonghua C, Li Sheng SfalseERK binding protein identificationIdentification of the ERK binding protein in regenerated legThu Mar 07 00:00:00 GMT 2024PXD050429697838507478