Arthur J Simon C
MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Front Biosci. 2008 May 1;13:5866-79. doi: 10.2741/3122.
Mitogen and stress activated protein kinase (MSK) 1 and 2 are nuclear serine/threonine protein kinases that are activated in vivo downstream of either the ERK1/2 or p38 mitogen activated protein kinase (MAPK) cascades. MSKs contain two kinase domains, an N-terminal kinase domain related to the AGC kinase family, and a C-terminal kinase domain related to the CaMK family. The upstream MAPK phosphorylates the C-terminal domain, which then phosphorylates and activates the N-terminal domain. Once activated, the N-terminal domain phosphorylates substrates. MSKs do not have a precisely defined substrate consensus sequence, however the do have a preference for a basic cluster prior to the phosphorylated residue. In cells MSKs phosphorylate several substrates including CREB, NFkB, HMGN1 and histone H3. The major role of MSKs appear to be in the regulation of immediate early (IE) genes, and consistent with this the transcription of several CRE dependent IE genes is compromised in MSK knockouts. The physiological roles of MSKs still remain to be completely determined, however recent work has suggested a role for MSKs in neuronal synaptic plasticity and in regulating cytokine production in the innate immune system.
丝裂原和应激激活蛋白激酶（MSK）1和2是核丝氨酸/苏氨酸蛋白激酶，在体内可被细胞外信号调节激酶1/2（ERK1/2）或p38丝裂原激活蛋白激酶（MAPK）级联反应下游激活。MSK包含两个激酶结构域，一个与AGC激酶家族相关的N端激酶结构域，以及一个与钙/钙调蛋白依赖性蛋白激酶（CaMK）家族相关的C端激酶结构域。上游的MAPK使C端结构域磷酸化，进而使N端结构域磷酸化并激活。一旦被激活，N端结构域就会使底物磷酸化。MSK没有精确界定的底物共有序列，不过它们确实偏好磷酸化残基之前的碱性簇。在细胞中，MSK使多种底物磷酸化，包括cAMP反应元件结合蛋白（CREB）、核因子κB（NFkB）、高迁移率族蛋白N1（HMGN1）和组蛋白H3。MSK的主要作用似乎是调节立即早期（IE）基因，与此一致的是，在MSK基因敲除的情况下，几种CRE依赖性IE基因的转录会受到影响。MSK的生理作用仍有待完全确定，不过最近的研究表明，MSK在神经元突触可塑性以及调节固有免疫系统中的细胞因子产生方面发挥作用。
