Taxonomic distribution of proteins containing MAPKK1_Int domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing MAPKK1_Int domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes.

Kurzbauer R, Teis D, de Araujo ME, Maurer-Stroh S, Eisenhaber F, Bourenkov GP, Bartunik HD, Hekman M, Rapp UR, Huber LA, Clausen T
Proc Natl Acad Sci U S A. 2004; 101: 10984-9

Signaling pathways in eukaryotic cells are often controlled by the formation ofspecific signaling complexes, which are coordinated by scaffold and adaptorproteins. Elucidating their molecular architecture is essential to understand thespatial and temporal regulation of cellular signaling. p14 and MP1 form a tight(K(d) = 12.8 nM) endosomal adaptor/scaffold complex, which regulatesmitogen-activated protein kinase (MAPK) signaling. Here, we present the 1.9-Acrystal structure of a biologically functional p14/MP1 complex. The overalltopology of the individual MP1 and p14 proteins is almost identical, having acentral five-stranded beta-sheet sandwiched between a two-helix and a one-helixlayer. Formation of the p14/MP1 heterodimer proceeds by beta-sheet augmentationand yields a unique, almost symmetrical, complex with several potentialprotein-binding sites on its surface. Mutational analysis allowed identification of the p14 endosomal adaptor motif, which seems to orient the complex relative tothe endosomal membrane. Two highly conserved and hydrophobic protein-bindingsites are located on the opposite "cytoplasmic" face of the p14/MP1 heterodimerand might therefore function as docking sites for the target proteinsextracellular regulated kinase (ERK) 1 and MAPK/ERK kinase 1. Furthermore,detailed sequence analyses revealed that MP1/p14, together with profilins, definea protein superfamily of small subcellular adaptor proteins, named ProflAP. Takentogether, the presented work provides insight into the spatial regulation of MAPKsignaling, illustrating how p14 and MP1 collaborate as an endosomaladaptor/scaffold complex.