Doublecortin kinase-2, a novel doublecortin-related protein kinase associated with terminal segments of axons and dendrites.
The microtubule (MT)-associated DCX protein plays an essential role in the development of the mammalian cerebral cortex. We report on the identification of a protein kinase, doublecortin kinase-2 (DCK2), with a domain (DC) highly homologous to DCX. DCK2 has MT binding activity associated with its DC domain and protein kinase activity mediated by a kinase domain, organized in a structure in which the two domains are functionally independent. Overexpression of DCK2 stabilizes the MT cytoskeleton against cold-induced depolymerization. Autophosphorylation of DCK2 strongly reduces its affinity for MTs. DCK2 and DCX mRNAs are nervous system-specific and are expressed during the period of cerebrocortical lamination. DCX is down-regulated postnatally, whereas DCK2 persists in abundance into adulthood, suggesting that the DC sequence has previously unrecognized functions in the mature nervous system. In sympathetic neurons, DCK2 is localized to the cell body and to the terminal segments of axons and dendrites. DCK2 may represent a phosphorylation-dependent switch for the reversible control of MT dynamics in the vicinity of neuronal growth cones.
Edelman
Arthur M
AM
Department of Pharmacology and Toxicology, State University of New York, Buffalo, New York 14214, USA.
Kim
Woo-Yang
WY
Higgins
Dennis
D
Goldstein
Elaine G
EG
Oberdoerster
Michele
M
Sigurdson
Wade
W
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002384:Catalysis; D002540:Cerebral Cortex / Q000378:metabolism; D003001:Cloning, Molecular; D003080:Cold Temperature; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D003712:Dendrites / Q000378:metabolism*; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D015536:Down-Regulation; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009420:Nervous System / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016366:Open Reading Frames; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
D018076:DNA, Complementary; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D012333:RNA, Messenger; D012313:RNA; D005982:Glutathione Transferase; D011494:Protein Kinases; D000089742:Doublecortin-Like Kinases; C498880:Dclk2 protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases