Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase.
Here we characterize a novel neuronal kinase, cyclin-dependent kinase 5 (cdk5)/p35-regulated kinase (cprk). Cprk is a member of a previously undescribed family of kinases that are predicted to contain two N-terminal membrane-spanning domains and a long C terminus, which harbors a dual-specificity serine/threonine/tyrosine kinase domain. Cprk was isolated in a yeast two-hybrid screen using the neuronal cdk5 activator p35 as "bait." Cprk interacts with p35 in the yeast-two hybrid system, binds to p35 in glutathione S-transferase fusion pull-down assays, and colocalizes with p35 in cultured neurons and transfected cells. In these cells, cprk is present with p35 in the Golgi apparatus. Cprk is expressed in a number of tissues but is enriched in brain and muscle and within the brain is found in a wide range of neuronal populations. Cprk displays catalytic activity in in vitro kinase assays and is itself phosphorylated by cdk5/p35. Cdk5/p35 inhibits cprk activity. Cdk5/p35 may therefore regulate cprk function in the brain.
Kesavapany
Sashi
S
Departments of Neuroscience and Neurology, The Institute of Psychiatry, Kings College London, London SE5 8AF, United Kingdom.
Lau
Kwok-Fai
KF
Ackerley
Steven
S
Banner
Steven J
SJ
Shemilt
Stephen J A
SJ
Cooper
Jonathan D
JD
Leigh
P Nigel
PN
Shaw
Christopher E
CE
McLoughlin
Declan M
DM
Miller
Christopher C J
CC
D000818:Animals; D001921:Brain / Q000201:enzymology; D016466:CHO Cells; D019556:COS Cells; D002462:Cell Membrane / Q000201:enzymology*; D002478:Cells, Cultured; D006224:Cricetinae; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009928:Organ Specificity; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C089495:neuronal Cdk5 activator (p25-p35); D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases