Cyclin-dependant kinases kinase activation

Figure 36-21. Schematic illustration of the points during the mammalian cell cycle during which the indicated cyclins and cyclin-dependent kinases are activated. The thickness of the various colored lines is indicative of the extent of activity.

Kanungo J, Zheng YL, Amin ND, Kaur S, Ramchandran R, Pant HC (2009) Specific inhibition of cyclin-dependent kinase 5 activity induces motor neuron development in vivo. Biochem Biophys Res Commun 386 263-267... 

FIGURE 12-44 Regulation of CDK by phosphorylation and proteolysis. (a) The cyclin-dependent protein kinase activated at the time of mitosis (the M phase CDK) has a "T loop" that can fold into the substrate-binding site. When Thr150 in the T loop is phosphorylated, the loop moves out of the substrate-binding site, activating the CDK... 

Kruggel S, Lemcke T (2009) Generation and evaluation of a homology model of PfGSK-3. Arch Pharm (Weinheim) 342(6) 327-332 Bracchi-Ricard V, Barik S, Delvecchio C et al (2000) PfPK6, a novel cyclin-dependent kinase/mitogen-activated protein kinase-related protein kinase from Plasmodium falciparum. Biochem J 347(Pt l) 255-263... 

Z5. Zhuang, S. H., and Burnstein, K. L., Antiproliferative effect of la,25-dihidroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology 139, 1197-1207 (1998). 

Cho DH, Lee EJ, Kwon KJ, Shin CY, Song KH, Park JH et al (2013) Troglitazone, a thiazolidinedione, decreases tau phosphorylation through the inhibition of cyclin-dependent kinase 5 activity in SH-SY5Y neuroblastoma cells and primary neurons. J Neurochem 126 685-695... 

A sequence of cyclin-cyclin dependent kinases (Cdk) activities triggers the orderly progression of cell-... 

How is replication tied to cell division Replication is tied to cell division by several proteins including the origin recognition complex, replication activator protein, and rep-hcation licensing factors. The process is controlled by cyclins, proteins produced during the Gj and S phases that bind to cyclin-dependent kinases and activate replication. 

It is well known that 2,6-diheteroaryl-containing pyridines display important biological properties such as antitumor and cyclin-dependent kinase inhibitory activities. Also, the introduction of ferf-butyl group into some heterocycles can greatly enhance their biological activity. Recently, Vang et al. [99] described a facile ultrasound-assisted synthesis of new 2,6-bis(5-fcrf-butyl-benzo[fc]furan-2-ylcarbonyl)pyridines from 2,6-bis(bromoacetyl)pyridine with f-butyl-substituted salicylaldehydes in acetonitrile in the presence of nontoxic and inexpensive catalyst as PEG-400. The new heterocyclic compounds were synthesized in short reaction times under mild reaction conditions with satisfactory yields. 

Cell-cycle arrest in G2/M phase reduction of cyclin-dependent kinases caspase activation apoptotic... 

Ubeda, M Rukstalis, J.M., and Habener, J.F. (2006) Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity. J. Biol. Chem., 281,28858-28864. 

Figure 13.30 Ribbon diagram of the structure of Src tyrosine kinase. The structure is divided in three units starting from the N-terminus an SH3 domain (green), an SH2 domain (blue), and a tyrosine kinase (orange) that is divided into two domains and has the same fold as the cyclin dependent kinase described in Chapter 6 (see Figure 6.16a). The linker region (red) between SH2 and the kinase is bound to SH3 in a polyproline helical conformation. A tyrosine residue in the carboxy tail of the kinase is phosphorylated and bound to SH2 in its phosphotyrosine-binding site. A disordered part of the activation segment in the kinase is dashed. (Adapted from W. Xu et al.. Nature 385 595-602, 1997.)...

A number of kinase structures have been determined in various catalytic states. For example, structures of the cyclin-dependent kinase, CDK2, in its inactive state and in a partially active state after cyclin binding have been discussed in Chapter 6. The most thoroughly studied kinase is the cyclic AMP-dependent protein kinase the structure of both the inactive and the active... 

Cell Cycle Control. Figure 1 Cell cycle regulation by Cyclin dependent kinases (CDKs). Different cyclins bound to different CDKs promote the transition from one cell cycle phase into another. CDK-dependent phosphorylation of Rb is required to release active E2F transcription factors, which promotes entry into S phase. 

Desai, D Gu, Y and Morgan, D. O. (1992). Activation of human cyclin-dependent kinases in vitro. Mol. Biol. Cell 3 571-582. 

Sebastian, B., Kakizuka, A., and Hunter, T. (1993). Cdc2M2 activation of cyclin-dependent kinase by dephosphorylation of threonine-14 and tyrosine-15 Proc. Natl. Acad. Sci. USA 90 3521-3524. 

CDK, cyclin-dependent kinase ERK, extracellular signal-regulated kinase GRK, G protein receptor kinase JNK, Jun kinase MAP kinase, mitogen activated protein kinase MEK, MAP kinase and ERK kinases RSK, ribosomal S6 kinase, GSK, glycogen synthase kinase SAPK, stress-activated protein kinase SEK, SAPK kinase. 

---