Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase.
The several hundred members of the eukaryotic protein kinase superfamily characterized to date share a similar catalytic domain structure, consisting of 12 conserved subdomains. Here we report the existence and wide occurrence in eukaryotes of a protein kinase with a completely different structure. We cloned and sequenced the human, mouse, rat, and Caenorhabditis elegans eukaryotic elongation factor-2 kinase (eEF-2 kinase) and found that with the exception of the ATP-binding site, they do not contain any sequence motifs characteristic of the eukaryotic protein kinase superfamily. Comparison of different eEF-2 kinase sequences reveals a highly conserved region of approximately 200 amino acids which was found to be homologous to the catalytic domain of the recently described myosin heavy chain kinase A (MHCK A) from Dictyostelium. This suggests that eEF-2 kinase and MHCK A are members of a new class of protein kinases with a novel catalytic domain structure.
Ryazanov
A G
AG
Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA. ryazanag@umdnj.edu
Ward
M D
MD
Mendola
C E
CE
Pavur
K S
KS
Dorovkov
M V
MV
Wiedmann
M
M
Erdjument-Bromage
H
H
Tempst
P
P
Parmer
T G
TG
Prostko
C R
CR
Germino
F J
FJ
Hait
W N
WN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000201:enzymology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D004023:Dictyostelium / Q000201:enzymology; D054736:Elongation Factor 2 Kinase; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D015800:Protozoan Proteins; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012156:Reticulocytes / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D017931:DNA Primers; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; C517689:EEF2K protein, human; C517691:Eef2k protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517690:Eef2k protein, mouse; D054736:Elongation Factor 2 Kinase; C033142:myosin-heavy-chain kinase