Orphan kinases turn eccentric: a new class of cyclin Y-activated, membrane-targeted CDKs.
PCTAIRE kinases (PCTK) are a highly conserved, but poorly characterized, subgroup of cyclin-dependent kinases (CDK). They are characterized by a conserved catalytic domain flanked by N- and C-terminal extensions that are involved in cyclin binding. Vertebrate genomes contain three highly similar PCTAIRE kinases (PCTK1,2,3, a.k.a., CDK16,17,18), which are most abundant in post-mitotic cells in brain and testis. Consistent with this restricted expression pattern, PCTK1 (CDK16) has recently been shown to be essential for spermatogenesis. PCTAIREs are activated by cyclin Y (CCNY), a highly conserved single cyclin fold protein. By binding to N-myristoylated CCNY, CDK16 is targeted to the plasma membrane. Unlike conventional cyclin-CDK interactions, binding of CCNY to CDK16 not only requires the catalytic domain, but also domains within the N-terminal extension. Interestingly, phosphorylation within this domain blocks CCNY binding, providing a novel means of cyclin-CDK regulation. By using these functional characteristics, we analyzed "PCTAIRE" sequence containing protein kinase genes in genomes of various organisms and found that CCNY and CCNY-dependent kinases are restricted to eumetazoa and possibly evolved along with development of a central nervous system. Here, we focus on the structure and regulation of PCTAIREs and discuss their established functions.
Division of Molecular Pathophysiology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
Petra
P
Mikolcevic
Johannes
J
Rainer
Stephan
S
Geley
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D013737:Testis / Q000378:metabolism
C543319:CCNY protein, human; D016213:Cyclins; D018844:Cyclin-Dependent Kinases; C089463:PCTAIRE-1 protein kinase; C109207:PCTAIRE-2 protein kinase; C089464:PCTAIRE-3 protein kinase