description
MAPK6 and MAPK4 (also known as ERK3 and ERK4) are vertebrate-specific atypical MAP kinases. Atypical MAPK are less well characterized than their conventional counterparts, and are generally classified as such based on their lack of activation by MAPKK family members. Unlike the conventional MAPK proteins, which contain a Thr-X-Tyr motif in the activation loop, MAPK6 and 4 have a single Ser-Glu-Gly phospho-acceptor motif (reviewed in Coulombe and Meloche, 2007; Cargnello et al, 2011). MAPK6 is also distinct in being an unstable kinase, whose turnover is mediated by ubiquitin-dependent degradation (Coulombe et al, 2003; Coulombe et al, 2004). The biological functions and pathways governing MAPK6 and 4 are not well established. MAPK6 and 4 are phosphorylated downstream of class I p21 activated kinases (PAKs) in a RAC- or CDC42-dependent manner (Deleris et al, 2008; Perander et al, 2008; Deleris et al, 2011; De La Mota-Peynado et al, 2011). One of the only well established substrates of MAPK6 and 4 is MAPKAPK5, which contributes to cell motility by promoting the HSBP1-dependent rearrangement of F-actin (Gerits et al, 2007; Kostenko et al, 2009a; reviewed in Kostenko et al, 2011b). The atypical MAPKs also contribute to cell motility and invasiveness through the NCOA3:ETV4-dependent regulation of MMP gene expression (Long et al, 2012; Yan et al, 2008; Qin et al, 2008). Both of these pathways may be misregulated in human cancers (reviewed in Myant and Sansom, 2011; Kostenko et al, 2012

external resources
NCBI:1269506
REACTOME:R-HSA-5687128
PUBMED:18644862
PUBMED:22800433
PUBMED:19166925
PUBMED:12808096
PUBMED:18248330
PUBMED:20849292
PUBMED:21329875
PUBMED:21177870
PUBMED:17161475
PUBMED:18593949
PUBMED:21372320
PUBMED:18720373
PUBMED:17947239
PUBMED:15226418
PUBMED:22505454

genes
CCND3 , CDK1 , SEPT7 , CDC42 , ETV4 , FOXO1 , FOXO3 , HSPB1 , DNAJB1 , JUN , MOV10 , MYC , PAK1 , PAK2 , PAK3 , PRKACA , PRKACB , PRKACG , MAPK4 , MAPK6 , PSMA1 , PSMA2 , PSMA3 , PSMA4 , PSMA5 , PSMA6 , PSMA7 , PSMB1 , PSMB2 , PSMB3 , PSMB4 , PSMB5 , PSMB6 , PSMB7 , PSMB8 , PSMB9 , PSMB10 , PSMC1 , PSMC2 , PSMC3 , PSMC4 , PSMC5 , PSMC6 , PSMD1 , PSMD2 , PSMD3 , PSMD4 , PSMD5 , PSMD7 , PSMD8 , PSMD9 , PSMD10 , PSMD11 , PSMD12 , PSMD13 , PSME1 , PSME2 , RAC1 , RAG1 , RAG2 , RPS27A , UBA52 , UBB , UBC , XPO1 , SEM1 , NCOA3 , MAPKAPK5 , CDC14B , CDC14A , KALRN , PSMF1 , PSMD6 , PSME3 , PSMD14 , CDC42EP2 , CDC42EP3 , IGF2BP1 , TNRC6B , PSME4 , AGO1 , AGO2 , TNRC6A , TNRC6C , PSMB11 , PSMA8 , CDC42EP5 , AGO3 , AGO4 , C7orf76 , LOC100506136 ,