Kinase Family PKG
Kinase Classification: Group AGC: Family PKG
Protein Kinase G (PKG) is related to PKA and PKC, but is typically activated by cGMP rather than cAMP (PKA) or Diacyl Glycerol and calcium (PKC).
Domain Organization
Most PKG have an N-terminal homodimerization/protein interaction region, followed by pair of cNMP_binding (cyclic nucleotide binding) domains, then a kinase domain and a pkinase_C (protein kinase C-terminal) domain. Binding of cGMP to the cNMP_binding domains relieves inhibition of the catalytic domain. cNMP_binding domains are not found in other major Group AGC families, but a similar pair of cNMP_binding domains is seen in the regulatory subunits of PKA, so what is a single polypeptide in PKG is split into two in PKA.
Evolution
PKG is found in all animals tested, including human (PKG1 and PKG2), Drosophila (for, Pkg21S, CG4839) and C. elegans (egl-4, pkg-2).
. Possible PKGs are found in other lineages, including algae (but not higher plants), ciliates, and apixomplexans. These non-animals often have 3 or 4 cNMP-binding domains, and their kinase domains alone don't mark them as clear orthologs of animal PKGs - the classification rests on the presence of the cNMP-binding domain. A few other kinases also have the cNMP-binding, including two Leishmania STE-group kinases, two distinct Tetrahymena kinases and an LRRK kinase in Dictyostelium. Higher plants....????
Paramecium contains at least one cGMP-responsive kinase, though it has not been cloned [1], and PKA and PKG activities could be biochemically distinguished [2].
Functions
Drosophila PKG forager (for) is well studied for its effect on foraging behavior: different alleles of for drive flies to look widely for food or stay close to home [3]. A similar phenotype was seen in the C. elegans PKG, egl-4, and in other insects and mammals [4].
Human PKG is known to modulate the nitrous oxide (NO) signaling pathway involved in smooth muscle relaxation [5], in platelet function
Both C. elegans PKGs, egl-4 and pkg-2 are genetically implicated in response to serotonin [6], and both serotonin and egl-4 are implicated in egg-laying.
References
- Miglietta LA and Nelson DL. A novel cGMP-dependent protein kinase from Paramecium. J Biol Chem. 1988 Nov 5;263(31):16096-105.
- Mason PA and Nelson DL. Cyclic AMP-dependent protein kinases of Paramecium. II. Catalytic and regulatory properties of type II kinase from cilia. Biochim Biophys Acta. 1989 Jan 17;1010(1):116-21. DOI:10.1016/0167-4889(89)90191-2 |
- Sokolowski MB. Drosophila: genetics meets behaviour. Nat Rev Genet. 2001 Nov;2(11):879-90. DOI:10.1038/35098592 |
- Kaun KR and Sokolowski MB. cGMP-dependent protein kinase: linking foraging to energy homeostasis. Genome. 2009 Jan;52(1):1-7. DOI:10.1139/G08-090 |
- Lincoln TM, Dey N, and Sellak H. Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol (1985). 2001 Sep;91(3):1421-30. DOI:10.1152/jappl.2001.91.3.1421 |
