TABLE 1.

Physiological roles of the MAPKAPKs

MAPKAPKGene symbolAlternate name(s)Human gene locationAssociated disease(s) (reference[s])Phenotype(s) of knockout mouse (reference[s])
RSK1Rps6ka1HU-1, MAPKAP-K1A, S6K-alpha 1, p90RSK11p36-p35Expressed at high level in breast and prostate tumors (65, 339)Viable (101)
RSK2Rps6ka3HU-3, MAPKAP-K1B, MRX19, S6K-alpha 3, ISPK-1, p90RSK2Xp22.13Coffin-Lowry syndrome (370), expressed at a higher level in breast and prostate tumors (65, 339)Viable and fertile, but knockout animals weigh 10% less than wild-type counterparts (99); reduction in adipose mass, as well as reduced serum leptin levels (103); impaired cognition and coordination skills (271); impaired T-lymphocyte activation (216)
RSK3Rps6ka2HU-2, MAPKAP-K1C, S6K-alpha 2, p90RSK36q27Potential tumor suppressor in ovarian cancer (28), RSK3 mutations are common in cancer (136)Viable (101)
RSK4Rps6ka6S6K-alpha 6, p90RSK4Xq21Possible role in nonspecific X-linked mental retardation (415), aberrant expression in breast cancer (362)Developmental defects (74)
MSK1Rps6ka5MSPK1, RLPK14q31-q32.1None reportedNo obvious phenotype (15)
MSK2Rps6ka4RSK-B11q11-q13Located in the locus of Bardet-Biedl syndrome (437)MSK2 and MSK1/2 double knockouts have no obvious phenotype (398); MSK1/2 play a negative role in innate immune system signaling (10)
MNK1Mknk11p34.1None reportedNo obvious phenotype (373)
MNK2Mknk219p13.3None reportedNo obvious phenotype (373)
MK2Mapkapk2MAPKAP-K21q32.1None reportedKnockout mice show increased resistance to endotoxic shock and increased susceptibility to infections (195, 211)
MK3Mapkapk3MAPKAP-K3, 3pK3p21.2Commonly deleted in small cell lung cancer (334)No obvious phenotype; deletion of MK3 worsens the phenotype of the MK2 knockout mouse (292)
MK5Mapkapk5MAPKAP-K5, PRAK12q24.12None reportedNo obvious phenotype (331); MK5-deficient mice are more susceptible to skin cancer (351)