title: The long form of CDK2 arises via alternative splicing and forms an active protein kinase with cyclins A and E.
abstract: We have reinvestigated the long form of cyclin-dependent kinase (CDK)2 that is expressed in many rodent cells. We show that the mRNA encoding CDK2L arises by alternative splicing and that the encoded protein can bind to, and be activated by, cyclins A and E. The complex of CDK2L with cyclin A has about half the specific activity of the equivalent CDK2-cyclin A complex. Also, CDK2L--cyclin A is inhibited to the same extent and by the same concentrations of p21(CIP1) as CDK2--cyclin A. The nucleotide sequences of intron V in the human and murine CDK2 genes, where the sequences encoding the 48-residue insert in CDK2L are located, show very high conservation in the position of the alternatively spliced exon and its surroundings. Despite this, we were not able to detect significant expression of CDK2L in human cell lines, although a low level is expressed in COS-1 cells from monkeys.
authors.affiliation: Paul Scherrer Institute, Institute for Medical Radiobiology, 5232 Villigen-PSI, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Ellenrieder
authors.forename: B
authors.initials: B
authors.lastname: Bartosch
authors.forename: G Y
authors.initials: GY
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Murphy
authors.forename: C
authors.initials: C
authors.lastname: Sweeney
authors.forename: M
authors.initials: M
authors.lastname: Hergersberg
authors.forename: M
authors.initials: M
authors.lastname: Carrington
authors.forename: R
authors.initials: R
authors.lastname: Jaussi
authors.forename: T
authors.initials: T
authors.lastname: Hunt
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D042846:CDC2-CDC28 Kinases; D019556:COS Cells; D002453:Cell Cycle; D002460:Cell Line; D002522:Chlorocebus aethiops; D019925:Cyclin A / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D016213:Cyclins; D004789:Enzyme Activation; D004791:Enzyme Inhibitors; D006801:Humans; D007527:Isoenzymes; D051379:Mice; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D019925:Cyclin A; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases