Comparative analysis of docking motifs in MAP-kinases and nuclear receptors.
Nuclear receptor (NR) agonists induce activation of mitogen-activated protein kinases (MAPK) through an yet unknown rapid non-genomic mechanism. Vice versa, NR are targets for phosphorylation by MAPK. By multiple alignment of the amino acid sequences and comparative analysis of the secondary and tertiary structures we identified four peptides in MAPK with similarity to bona fide protein-protein-interaction motifs in NR. In both molecule species, these motifs mediate selective docking to dimerization partners, coregulators or phosphoacceptors. We therefore propose that similar motifs may direct the site-specific association of NR with MAPK. Based on mutual allosteric interactions within a kinase-receptor complex, we discuss a novel principle how NR-agonists may regulate kinase activity and thus expression of hormone-dependent genes.
Burgermeister
Elke
E
Dept. of Biological Regulation, The Weizmann Institute of Science, I-76100 Rehovot, Israel. elke.burgermeister@weizmann.ac.il
Lanzendoerfer
Martin
M
Scheuer
Werner
W
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment
D008024:Ligands; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D020928:Mitogen-Activated Protein Kinases