Cyclin-dependent Kinase 5 Regulates MAPK/ERK Signaling In The Skin Of Mice

Cyclin-dependent kinase 5(CDK5)is a proline-directed serine/threonine kinase that has been shown to play an important role in many tissues other than the nervous system.We previously reported that CDK5 showed differential expression in the chromosomal transcriptome profiles alpaca skins with different hair colors and the decreased expression of CDK5 causes the lightened hair color phenotype.From the mRNA expression profile in skins of CDK5 knockdown mice,the mitogen-activated protein kinase(MAPK)pathway was found to be regulated.Here,real-time quantitative PCR,co-immunoprecipitation and Western blot were used to analyze the effect of CDK5 knockdown on MAPK pathway in mice.The results were as follows:1.CDK5 mRNA expression was significantly decreased in CDK5 knockout mice skin s(P<0.001).The protein expression of phosphorylated CDK5 was significantly decreased(P<0.001),while the total CDK5 protein expression was not significant.Compared to wild type mouse skin,CDK7 mRNA expression in CDK5 knockdown mice was significantly reduced(P<0.01).Co-immunoprecipitation experiments showed that CDK5 interacts with CDK7.In addition,CDK7 protein expression was significantly greater in wild-type mice and significantly lower in the skin of CDK5 knock-out mice(P<0.01).2.On the MAPK pathway,compared to wild-type mouse skin,the expression level of MAP3K6 mRNA in the skin of CDK5 knockout mice was significantly reduced(P<0.001).The MAP3K6 protein was mainly localized at the basal surface of CDK5 knockout mice and was significantly more abundant than wild type mice;The expression of MEKI mRNA in CDK5 knockout mice was significantly lower than that in wild type mice(P<0.01).There was no significant change in total MEK1 protein expression in CDK5 knockout mice,whereas CDK5 knockout mice were down-regulated in p-MEK1 expression in wild-type mice,with significant differences(P<0.05).The protein levels of MITF,p-ERK,MAP3K5,CREB and Dicer in CDK5 knockout mice were significantly lower than those in wild type mice(P<0.05;P<0.001).There is no significant difference in changes.The expression of miR-143 in the skin of CDK5 knockout mice was significantly up-regulated compared to wild-type mice(P<0.05)3.Compared to wild-type mouse skin,the production of melanin in the skin of CDK5 knockout mice was lower than that in wild type mice(P<0.001),and the yield of brown melanin was increased(P<0.05).All together,CDK5 regulated MAPK pathway through MAP3K6 by binding with CDK7,resulting in the eu-and phew-melanin production.