Kinase Group AGC

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Kinase Classification: AGC Group

The AGC group is named after the protein kinase A, G, and C families (PKA, PKC, PKG) which have a long history as cytoplasmic serine/threonine kinases that are regulated by secondary messengers such as cyclic AMP (PKA) or lipids (PKC). The group consits of 16 families, of which 8 are likely to have been in early eukaryotes, with another two (RSK, PKC) in the fungal/metazoan lineage and 6 more (PKG, PKN, DMPK, YANK, RSKR, RSKL) only found in metazoans. See also our annotated AGC tree, a general review of AGC kinases [1] and a sequence analysis of the group [2].

AGC kinase families

PKA

Protein Kinase A/ cyclic AMP-dependent protein kinase (cAPK), activated by cAMP production downstream of G protein coupled receptors, and other stimuli. Multiple members found in all eukaryotes.

PKC

Protein Kinase C. A large family responsive to lipid signaling.

PKG

Protein Kinase G, or cGMP-dependent protein kinase. Implicated in several functions, including smooth muscle and platelet biology and foraging behavior.

PKN

Protein Kinase N. Found in metazoans, with three copies in mammals, with only the mammalian PKN1 (PRK1) characterized. The C-terminal kinase domain is very similar to PKC, but these also have and N-terminal antiparallel coiled-coil structure (HR1 domain) that binds and is activated by Rho. This domain is also seen in the DMPK family and in the single yeast PKC gene (PKC1), which suggests a dual function for PKC1 (it also has the C1 and C2 domains typical of PKC).

PDK1

'Master Kinase' that activates most other AGC kinases. A key component in transducing signals from phosphoinsoitides (from Insulin and various growth signals) to several other AGC-Group kinases including Akt, SGK, PKC and RSK members, as well as mTOR.

AKT and SGK

Akt (also known as Protein Kinase B, PKB) is downstream of PDK1 in insulin and growth factor signaling. Akt proteins include lipid-binding PH domains, while the closely related SGK (Serum and Glucocortioid induced Kinases) kinases lack this domain.

RSK, RSKR, and RSKL

Ribosomal protein S6 Kinases. RSKL and RSKR are a poorly-examined metazoan families whose sequences are quite close to RSK. The three main subfamilies of RSK are p70, p90 (RSK) and MSK. The latter two each have secondary domains that belong to the CAMK group of kinases.

GRK

G-protein-coupled receptor kinases. As the name replies, they modulate GPCRs, including the rhodopsin light-sensitive GPCR, and a variety of neurotransmitter receptors.

NDR and MAST

Primordial families whose sequences are highly similar and sometimes difficult to distinguish. MAST kinases have two subfamilies: MASTL (MAST-like) and MAST. The MASTL kinases have a very long insert in the activation loop region (with patches of sequence conservation), but little sequence upstream or downstream of the kinase, while MAST kinases have long C-terminal extensions with known and novel domains.

DMPK

Named after the Myotonic Dystrophy Protein Kinase

YANK

A family about which so little is known, it stands for "Yet Another Novel Kinase". Animal-specific.

PTF

Includes plant phototrophin receptors and fungal flippase kinases


References

  1. Pearce LR, Komander D, and Alessi DR. The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol. 2010 Jan;11(1):9-22. DOI:10.1038/nrm2822 | PubMed ID:20027184 | HubMed [Pearce]
  2. Kannan N, Haste N, Taylor SS, and Neuwald AF. The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module. Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1272-7. DOI:10.1073/pnas.0610251104 | PubMed ID:17227859 | HubMed [Kannan]
All Medline abstracts: PubMed | HubMed