The alpha-kinases TRPM6 and TRPM7, but not eEF-2 kinase, phosphorylate the assembly domain of myosin IIA, IIB and IIC.
TRPM6 and TRPM7 encode channel-kinases. While these channels share electrophysiological properties and cellular functions, TRPM6 and TRPM7 are non-redundant genes raising the possibility that the kinases have distinct substrates. Here, we demonstrate that TRPM6 and TRPM7 phosphorylate the assembly domain of myosin IIA, IIB and IIC on identical residues. Whereas phosphorylation of myosin IIA is restricted to the coiled-coil domain, TRPM6 and TRPM7 also phosphorylate the non-helical tails of myosin IIB and IIC. TRPM7 does not phosphorylate eukaryotic elongation factor-2 (eEF-2) and myosin II is a poor substrate for eEF-2 kinase. In conclusion, TRPM6 and TRPM7 share exogenous substrates among themselves but not with functionally distant alpha-kinases.
Clark
Kristopher
K
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Middelbeek
Jeroen
J
Dorovkov
Maxim V
MV
Figdor
Carl G
CG
Ryazanov
Alexey G
AG
Lasonder
Edwin
E
van Leeuwen
Frank N
FN
D000595:Amino Acid Sequence; D002460:Cell Line; D054736:Elongation Factor 2 Kinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
D054736:Elongation Factor 2 Kinase; D018995:Myosin Heavy Chains; D024462:Myosin Type II; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels; C477830:MYH7b protein, human; C459082:TRPM6 protein, human; C517689:EEF2K protein, human; C486583:TRPM7 protein, human