MAP2K6

Abstract: Objective The aim of this study is to identify genomic regions or genes controlling growth traits in pigs Methods Using a panel of 54,148 single nucleotide polymorphisms (SNPs), we performed a genome-wide Association (GWA) study in 562 pure Yorshire pigs with four growth traits: average daily gain from 30 kg to 100 kg or 115 kg, and days to 100 kg or 115 kg Fixed and random model Circulating Probability Unification method was used to identify the associations between 54,148 SNPs and these four traits SNP annotations were performed through the Sus scrofa data set from Ensembl Bioinformatics analysis, including gene ontology analysis, pathway analysis and network analysis, was used to identify the candidate genes Results We detected 6 significant and 12 suggestive SNPs, and identified 9 candidate genes in close proximity to them (suppressor of glucose by autophagy [SOGA1], R-Spondin 2 [RSPO2], mitogen activated protein kinase kinase 6 [MAP2K6], phospholipase C beta 1 [PLCB1], rho GTPASE activating protein 24 [ARHGAP24], cytoplasmic polyadenylation element binding protein 4 [CPEB4], GLI family zinc finger 2 [GLI2], neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2 [NYAP2], and zinc finger protein multitype 2 [ZFPM2]) Gene ontology analysis and literature mining indicated that the candidate genes are involved in bone, muscle, fat, and lung development Pathway analysis revealed that PLCB1 and MAP2K6 participate in the gonadotropin signaling pathway and suggests that these two genes contribute to growth at the onset of puberty Conclusion Our results provide new clues for understanding the genetic mechanisms underlying growth traits, and may help improve these traits in future breeding programs

Abstract: Mitogen-activated protein kinase kinase 6 (MAP2K6) plays a crucial role in the p38 MAP kinase signal cascade that regulates various stress-induced responses and is associated with pathological conditions. The crystal structure of human non-phosphorylated MAP2K6 (npMAP2K6) complexed with an ATP analogue was determined at 2.6 A resolution and represents an auto-inhibition state of MAP2K6. Three characteristics of short α-helices configured in the activation loop region, termed activation helices (AH1, AH2 and AH3), are important in controlling the auto-inhibition mechanism. AH1 displaces the αC-helix, a component essential for forming the active configuration, away from the active site. AH1 and AH2 were found to enclose the γ-phosphate, the leaving group of ATP. A comparison with the related enzymes, MAP2K1 and MAP2K4 reveals that MAP2K6 has the unique auto-inhibition mechanism mediated by the three activation helices.

Abstract: MAP2K3 protein is mitogen-activated protein kinase belonging to the family of kinases involved in intracellular cell proliferation. The mammalian MAPK family that consists of ERK, p38 and JNK signalling pathway is showing a critical role in the regulation of cell proliferation. MAP2K3 and MAP2K6 are highly selective for p38 MAPKs which actively participate at check point controls and various stages of cell cycle at G0, G1/S and G2/M transitions by differential regulation of specific cyclin A or D1. In the present work, the 3D model of MAP2K3 protein is generated using comparative homology modelling techniques, minimized and validated. Active site of the protein is determined using various server tools and literature studies, for the prediction of important binding pockets to identify the putative active site. Virtual screening was carried out using chalcone library in Schrodinger suite to identify new lead molecules to knock down MAP2K3 target protein and inhibit cell proliferation. An Atomistic MD simulation of screened compound with MAP2K3 not only strengthens our findings but also identified the key interactions involved in protein-ligand complex in the dynamic environment.