D
IPR000961

AGC-kinase, C-terminal

InterPro entry
Short nameAGC-kinase_C
Overlapping
homologous
superfamilies
 
domain relationships

Description

The AGC (cAMP-dependent, cGMP-dependent and protein kinase C) protein kinase family embraces a collection of protein kinases that display a high degree of sequence similarity within their respective kinase domains. AGC kinase proteins are characterised by three conserved phosphorylation sites that critically regulate their function. The first one is located in an activation loop in the centre of the kinase domain. The two other phosphorylation sites are located outside the kinase domain in a conserved region on its C-terminal side, the AGC-kinase C-terminal domain. These sites serves as phosphorylation-regulated switches to control both intra- and inter-molecular interactions. Without these priming phosphorylations, the kinases are catalytically inactive
[2, 3, 4]
.

Several structures of the AGC-kinase C-terminal domain have been solved. The first phosphorylation site is located in a turn motif, the second one at the end of the domain in an hydrophobic pocket. In PKB the phosphorylated hydrophobic motif engages a hydrophobic groove within the N-lobe of the kinase domain which orders α helices close to the active site
[5]
.

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity
[6]
:


 * Serine/threonine-protein kinases
 * Tyrosine-protein kinases
 * Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)


Protein kinase function is evolutionarily conserved from Escherichia coli to human
[1]
. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation
[7]
. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved
[8]
, leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases
[9]
.

References

1.The protein kinase complement of the human genome. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. Science 298, 1912-34, (2002). View articlePMID: 12471243

2.Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Newton AC. Biochem. J. 370, 361-71, (2003). View articlePMID: 12495431

3.AGC protein kinase phosphorylation and protein kinase C. Parker PJ, Parkinson SJ. Biochem. Soc. Trans. 29, 860-3, (2001). View articlePMID: 11709088

4.PDK1, the master regulator of AGC kinase signal transduction. Mora A, Komander D, van Aalten DM, Alessi DR. Semin. Cell Dev. Biol. 15, 161-70, (2004). View articlePMID: 15209375

5.Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP. Yang J, Cron P, Good VM, Thompson V, Hemmings BA, Barford D. Nat. Struct. Biol. 9, 940-4, (2002). View articlePMID: 12434148

6.The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Hanks SK, Quinn AM, Hunter T. Science 241, 42-52, (1988). View articlePMID: 3291115

7.Evolution of protein kinase signaling from yeast to man. Manning G, Plowman GD, Hunter T, Sudarsanam S. Trends Biochem. Sci. 27, 514-20, (2002). View articlePMID: 12368087

8.High-throughput structural biology in drug discovery: protein kinases. Stout TJ, Foster PG, Matthews DJ. Curr. Pharm. Des. 10, 1069-82, (2004). View articlePMID: 15078142

9.Creating chemical diversity to target protein kinases. Li B, Liu Y, Uno T, Gray N. Comb. Chem. High Throughput Screen. 7, 453-72, (2004). View articlePMID: 15320712

GO terms

Cross References

Contributing Member Database Entries
This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.