+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Mechanisms of autoinhibition in cyclic nucleotide-dependent protein kinases

, : Mechanisms of autoinhibition in cyclic nucleotide-dependent protein kinases. Frontiers in Bioscience 7: D580-D592

Cyclic AMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) are autoinhibited through multiple interactions between their respective regulatory and catalytic domains. A large portion of this autoinhibition occurs through interactions between residues within the catalytic domain and those within either a substrate-like sequence (-RRXSX-) or pseudosubstrate sequence (-RRXAX-) in the regulatory domains. These contacts effectively inhibit catalysis by blocking substrate binding. Particularly important contacts involve the P-2, P-3, and P+1 residues where either serine, which is potentially autophosphorylated, or alanine occupies the P0 position. The primary sequence is apparently less important for autoinhibition in PKGs than in PKAs, and a conserved serine at P+2 in PKGs is important for autoinhibitory contacts. Elements outside the substrate-related sequences also contribute to autoinhibition in both PKA and PKG. For example, synthetic peptides with relatively short pseudosubstrate sequences are weak inhibitors; while heat-denatured RII subunit does not inhibit catalytic subunit, it is still rapidly autophosphorylated; and truncated PKGs lacking the substrate-like sequence are still partially autoinhibited. Thus, capacity for autoinhibition of PKA or PKG is provided by contacts involving direct interactions with the catalytic site and by contacts that stabilize an inactive conformation.


PMID: 11861209

Other references

Fries, J.Stephen; Trowbridge, J.H., 2003: Flume observations of enhanced fine-particle deposition to permeable sediment beds. Predictions of the deposition rate of fine particles are integral to the study of the transport of many constituents, including contaminants and organic matter. Generally, fine-particle deposition rates are assumed to be equivalent to the suspensi...

Lüderitz, B., 1991: Problems of long-term therapy and therapeutic damage considering the clinical aspects. Cardiology. Verhandlungen der Deutschen Gesellschaft für Innere Medizin 97: 34-43

Cole, L., 1984: Oregon vocational agriculture teacher placement and retention factors. Journal of the American Association of Teacher Educators in Agriculture 25(3): 2-12

Pathil, A.; Mueller, J.; Ludwig, J.M.; Wang, J.; Warth, A.; Chamulitrat, W.; Stremmel, W., 2015: Ursodeoxycholyl lysophosphatidylethanolamide attenuates hepatofibrogenesis by impairment of TGF-β1/Smad2/3 signalling. Chronic hepatic inflammation results in liver fibrosis. As effective anti-fibrogenic agents are lacking, we investigated ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), a synthetic bile acid-phospholipid conjugate with anti-inflammatory a...

Loening-Baucke, V.; Anuras, S., 1985: Effects of age and sex on anorectal manometry. We studied rectal and anal function in 18 healthy elderly and 18 healthy young adults using intraluminal pressure transducers and a rectal balloon. Both age groups consisted of nine females and nine males. Age did not affect anal length, highest a...

Cohen, M.; Shanks, W., 1953: An apparatus for intra-cavity administration of radioactive colloidal gold. British Journal of Radiology 26(312): 660-662

Labandeira, J.; Toribio, J., 2003: Reinstatement of dapsone following hypersensitivity. Acta Dermato-Venereologica 83(4): 314-315

Plaut, D., 1971: Timely topics in clinical chemistry 1970, a review. American Journal of Medical Technology 37(8): 338-348

Janicka Mazur, W.; Slota, E.; Willmann Wegrzyn, Z., 1976: The characteristic of the newly discovered allotype (K1) in fowls. A new blood serum protein antigen, K1, was discovered in 945 Cornish and 1285 White Plymouth Rock chicks. It is inherited independently of the previously discovered antigens K4, K5 and K6, and is determined by an autosomal dominant gene.

Chen, B.; Sysoeva, T.A.; Chowdhury, S.; Guo, L.; Nixon, B.Tracy., 2009: ADPase activity of recombinantly expressed thermotolerant ATPases may be caused by copurification of adenylate kinase of Escherichia coli. Except for apyrases, ATPases generally target only the gamma-phosphate of a nucleotide. Some non-apyrase ATPases from thermophilic microorganisms are reported to hydrolyze ADP as well as ATP, which has been described as a novel property of the ATP...