000148186 001__ 148186
000148186 005__ 20190316234745.0
000148186 022__ $$a0014-2956
000148186 0247_ $$2doi$$a10.1046/j.1432-1327.2001.02151.x
000148186 037__ $$aARTICLE
000148186 245__ $$aPfnek-1, a NIMA-related kinase from the human malaria parasite Plasmodium falciparum: Biochemical properties and possible involvement in MAPK regulation
000148186 269__ $$a2001
000148186 260__ $$c2001
000148186 336__ $$aJournal Articles
000148186 520__ $$aWe have cloned Pfnek-1, a gene encoding a novel protein kinase from the human malaria parasite Plasmodium falciparum. This enzyme displays maximal homology to the never-in-mitosis/Aspergillus (NIMA)/NIMA-like kinase (Nek) family of protein kinases, whose members are involved in eukaryotic cell division processes. Similar to other P. falciparum protein kinases and many enzymes of the NIMA/Nek family, Pfnek-1 possesses a large C-terminal extension in addition to the catalytic domain. Bacterially expressed recombinant Pfnek-1 protein is able to autophosphorylate and phosphorylate a panel of protein substrates with a specificity that is similar to that displayed by other members of the NIMA/Nek family. However, the FXXT motif usually found in NIMA/Nek protein kinases is substituted in Pfnek-1 by a SMAHS motif, which is reminiscent of a MAP/ERK kinase (MEK) activation site. Mutational analysis indicates that only one of the serine residues in this motif is essential for Pfnek-1 kinase activity in vitro. We show (a) that recombinant Pfnek-1 is able to specifically phosphorylate Pfmap-2, an atypical P. falciparum MAPK homologue, in vitro, and (b) that coincubation of Pfnek-1 and Pfmap-2 results in a synergistic increase in exogenous substrate labelling. This suggests that Pfnek-1 may be involved in the modulation of MAPK pathway output in malaria parasites. Finally, we demonstrate that recombinant Pfnek-1 can be used in inhibition assays to monitor the effect of kinase inhibitors, which opens the way to the screening of chemical libraries aimed at identifying potential new antimalarials.
000148186 6531_ $$aCell Cycle Proteins
000148186 700__ $$0243706$$g198457$$aDorin, D.
000148186 700__ $$aLe Roch, K.
000148186 700__ $$aSallicandro, P.
000148186 700__ $$aAlano, P.
000148186 700__ $$aParzy, D.
000148186 700__ $$aPoullet, P.
000148186 700__ $$aMeijer, L.
000148186 700__ $$aDoerig, C.$$g191299$$0243705
000148186 773__ $$j268$$tEuropean journal of biochemistry / FEBS$$k9$$q2600-8
000148186 8564_ $$uhttps://infoscience.epfl.ch/record/148186/files/Dorin-D_2001.pdf$$zn/a$$s778025$$yPublisher's version
000148186 909C0 $$xU12184$$0252274$$pINSERM-EPFL
000148186 909CO $$qGLOBAL_SET$$particle$$ooai:infoscience.tind.io:148186
000148186 937__ $$aEPFL-ARTICLE-148186
000148186 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000148186 980__ $$aARTICLE