如其名称，CDK的激酶调控活性依赖于週期素。在没有週期素的情况下，CDK几乎没有激酶活性，只有週期素-CDK复合物才是有活性的激酶。CDK磷酸化其底物的丝氨酸/苏氨酸残基，因此属于丝氨酸/苏氨酸激酶类。The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is [S/T*]PX[K/R], where S/T* is the phosphorylated serine or threonine, P is proline, X is any amino acid, K is lysine, and R is arginine 
|Cdk1||Cyclin B||M phase||None. ~E2.5.|
|Cdk2||Cyclin E||G1/S transition||Reduced size, imparted neural progenitor cell proliferation. Viable, but both males & females sterile.|
|Cdk2||Cyclin A||S phase, G2 phase|
|Cdk3||Cyclin C||G1 phase ?||No defects. Viable, fertile.|
|Cdk4||Cyclin D||G1 phase||Reduced size, insulin deficient diabetes. Viable, but both male & female infertile.|
|Cdk5||p35||Transcription||Severe neurological defects. Died immediately after birth.|
|Cdk6||Cyclin D||G1 phase|
|Cdk7||Cyclin H||CDK-activating kinase, transcription|
|Cdk8||Cyclin C||Transcription||Embryonic lethal|
|Cdk9||Cyclin T||Transcription||Embryonic lethal|
|Cdk11||Cyclin L||?||Mitotic defects. E3.5.|
|?||Cyclin F||?||Defects in extraembryonic tissues. E10.5.|
|G1||D, E||Cdk4, Cdk2, Cdk6|
|芽殖酵母||Cdk1||Cdc28||298||All cell-cycle stages|
|裂殖酵母||Cdk1||Cdc2||297||All cell-cycle stages|
|Cdk2||Cdc2c||314||G1/S, S, possibly M|
|Cdk4||Cdk4/6||317||G1, promotes growth|
|Cdk2||297||S, possibly M|
|Cdk2||298||G1, S, possibly M|
- CDK1; cyclin A, cyclin B
- CDK2; cyclin A, cyclin E
- CDK3; cyclin C
- CDK4; cyclin D1, cyclin D2, cyclin D3
- CDK5; CDK5R1, CDK5R2. See also CDKL5.
- CDK6; cyclin D1, cyclin D2, cyclin D3
- CDK7; cyclin H
- CDK8; cyclin C
- CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K
- CDK11 (CDC2L2) ; cyclin L
- CDK12 (CRKRS) ; cyclin L
- CDK13 (CDC2L5) ; cyclin L
CDK levels remains relatively constant throughout the cell cycle and most regulation is post-translational. Most knowledge of CDK structure and function is based on CDKs of S. pombe (Cdc2), S. cerevisiae (CDC28), and vertebrates (CDC2 and CDK2). The four major mechanisms of CDK regulation are cyclin binding, CAK phosphorylation, regulatory inhibitory phosphorylation, and binding of CDK inhibitory subunits (CKIs).
The active site, or ATP-binding site, of all kinases is a cleft between a small amino-terminal lobe and a larger carboxy-terminal lobe. The structure of human Cdk2 revealed that CDKs have a modified ATP-binding site that can be regulated by cyclin binding. Phosphorylation by CDK-activating kinase (CAK) at Thr 161 on the T-loop increases the complex activity. Without cyclin, a flexible loop called the activation loop or T-loop blocks the cleft, and the position of several key amino acid residues is not optimal for ATP-binding. With cyclin, two alpha helices change position to permit ATP binding. One of them, the L12 helix that comes just before the T-loop in the primary sequence, becomes a beta strand and helps rearrange the T-loop, so it no longer blocks the active site. The other alpha helix called the PSTAIRE helix rearranges and helps change the position of the key amino acid residues in the active site.
There is considerable specificity in which cyclin binds with CDK. Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates. Cyclins can directly bind the substrate or localize the CDK to a subcellular area where the substrate is found. Substrate specificity of S cyclins is imparted by the hydrophobic batch (centered on the MRAIL sequence), which has affinity for substrate proteins that contain a hydrophobic RXL (or Cy) motif. Cyclin B1 and B2 can localize Cdk1 to the nucleus and the Golgi, respectively, through a localization sequence outside the CDK-binding region.
Full kinase activity requires an activating phosphorylation on a threonine adjacent to the active site. The identity of the CDK-activating kinase (CAK) that performs this phosphorylation varies across the model organisms. The timing of this phosphorylation varies as well. In mammalian cells, the activating phosphorylation occurs after cyclin binding. In yeast cells, it occurs before cyclin binding. CAK activity is not regulated by known cell-cycle pathways and cyclin binding is the limiting step for CDK activation.
Unlike activating phosphorylation, CDK inhibitory phosphorylation is vital for regulation of the cell cycle. Various kinases and phosphatases regulate their phosphorylation state. One of the kinases that place the tyrosine phosphate is Wee1, a kinase conserved in all eukaryotes. Fission yeast also contains a second kinase Mik1 that can phosphorylate the tyrosine. Vertebrates contain a different second kinase called Myt1 that is related to Wee1 but can phosphorylate both the threonine and the tyrosine. Phosphatases from the Cdc25 family dephosphorylate both the threonine and the tyrosine.
CDK抑制因子（CKI）是一类与周期素-CDK复合物相互作用来阻断其激酶活性的蛋白 usually during G1 or in response to signals from the environment or from damaged DNA. In animal cells, there are two major CKI families: the INK4 family and the CIP/KIP family. The INK4 family proteins are strictly inhibitory and bind CDK monomers. Crystal structures of CDK6-INK4 complexes show that INK4 binding twists the CDK to distort cyclin binding and kinase activity. The CIP/KIP family proteins bind both the cyclin and the CDK of a complex and can be inhibitory or activating. CIP/KIP family proteins activate cyclin D and CDK4 or CDK6 complexes by enhancing complex formation.
In yeast and Drosophila, CKIs are strong inhibitors of S- and M-CDK, but do not inhibit G1/S-CDKs. During G1, high levels of CKIs prevent cell cycle events from occurring out of order, but do not prevent transition through the Start checkpoint, which is initiated through G1/S-CDKs. Once the cell cycle is initiated, phosphorylation by early G1/S-CDKs leads to destruction of CKIs, relieving inhibition on later cell cycle transitions. In mammalian cells, the CKI regulation works differently. Mammalian protein p27 (Dacapo in Drosophila) inhibits G1/S- and S-CDKs, but does not inhibit S- and M-CDKs.
表4： CDK抑制性药物 
|Flavopiridol (Alvocidib)||1, 2, 4, 6, 7, 9|
|Olomoucine||1, 2, 5|
|Roscovitine||1, 2, 5|
|Purvalanol||1, 2, 5|
|Paullones||1, 2, 5|
|Butryolactone||1, 2, 5|
- ^ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 Morgan, David O. (2007). The Cell Cycle: Principles of Control. London: New Science Press, 1st ed.
- ^ Lee, Melanie; Nurse, Paul. (1987). "Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2." Nature 327:31-35.
- ^ 3.0 3.1 3.2 3.3 Morgan, David O. (1997) "Cyclin-Dependent Kinase: Engines, Clocks, and Microprocessors." Annual Review of Cell and Developmental Biology. 13:261-291.
- ^ 4.0 4.1 Satyanarayana, A; Kaldis. (2009). “Mammalian cell-cycle regulation: several Cdks, numerous cyclins, and diverse compensatory mechanisms” “Oncogene” 28:2925-2939
- ^ Morgan, David O. (1995). “Principles of CDK regulation.” “Nature” 374:131-133.
- ^ 6.0 6.1 Sausville, Edward A. (2002) “Complexities in the development of cyclin-dependent kinase inhibitor drugs” “Trends in Molecular Medicine” 8:S32-S37
- EC 188.8.131.52
- KEGG - Human Cell Cycle
- Loyer P, Trembley J, Katona R, Kidd V, Lahti J. Role of CDK/cyclin complexes in transcription and RNA splicing. Cell Signal. 2005, 17 (9): 1033–51. doi:10.1016/j.cellsig.2005.02.005. PMID 15935619.