Kinase Subfamily AFK

Kinase Classification: Group PKL: Family PIK: Subfamily AFK

Actin Fragmin Kinase is found in plants and some non-animal Unikonts. It has an unusual structure and is weakly related to the inositol kinase PI4K2.

Function

AFK was first detected in Physarum polycephalum, a slime mold distantly related to Dictyostelium. It phosphorylates actin on T202 and T203 when bound in complex with the gelsolin-like capping protein, fragmin [1]. A gain-of-function mutation in the phosphatase domain of the Arabidopsis AFK, phs1, is genetically linked to microtubule function [2] but not to actin. A partial loss of function mutation in phs1 also has a defect in abscisic acid signaling [3]. PHS1 physically interacts with the MAPK MPK18 and can dephosphorylate it [4].

Evolution

Homologs of Physarum AFK are found in other slime molds (4 in Dictyostelium) [5], in ciliates, and in non-animal holozoans (Monosiga, Salpingoeca, Capsaspora). In addition, AFK is found in algae and all land plants. Here's a partially-edited multiple sequence alignment: AFK alignment.

Domain Structure

Most AFK have a single, kinase, domain. Plant AFKs also have a DUSP phosphatase domain. A Paramecium AFK also has an ePK kinase domain fused to an AFK, but as this is not seen in other ciliates, it may be a gene prediction artefact. The sequence of the kinase domain is highly divergent from other PKLs, and it took the crystallization of the kinase domain to show that it was a PKL [6]. With additional AFK detectable by Blast, psi-blast can now link AFK to PI4K2 kinases and related bacterial kinases.

The catalytic loop of Physarum AFK is unusual in having an insert within the loop, changing DxxxxN to DVIVNNSDRLPIAWTNEGNLDN. This sequence is generally well conserved in most other AFK members, though the D is lost in Dictyostelium homologs, and an slightly upstream DxxxxN is just as well conserved, and might be catalytic (a similar situation is seen in Subfamily PI4K2).

References

1. Eichinger L, Bomblies L, Vandekerckhove J, Schleicher M, and Gettemans J. A novel type of protein kinase phosphorylates actin in the actin-fragmin complex. EMBO J. 1996 Oct 15;15(20):5547-56.
2. Naoi K and Hashimoto T. A semidominant mutation in an Arabidopsis mitogen-activated protein kinase phosphatase-like gene compromises cortical microtubule organization. Plant Cell. 2004 Jul;16(7):1841-53. DOI:10.1105/tpc.021865 |
3. Quettier AL, Bertrand C, Habricot Y, Miginiac E, Agnes C, Jeannette E, and Maldiney R. The phs1-3 mutation in a putative dual-specificity protein tyrosine phosphatase gene provokes hypersensitive responses to abscisic acid in Arabidopsis thaliana. Plant J. 2006 Sep;47(5):711-9. DOI:10.1111/j.1365-313X.2006.02823.x |
4. Walia A, Lee JS, Wasteneys G, and Ellis B. Arabidopsis mitogen-activated protein kinase MPK18 mediates cortical microtubule functions in plant cells. Plant J. 2009 Aug;59(4):565-75. DOI:10.1111/j.1365-313X.2009.03895.x |
5. Goldberg JM, Manning G, Liu A, Fey P, Pilcher KE, Xu Y, and Smith JL. The dictyostelium kinome--analysis of the protein kinases from a simple model organism. PLoS Genet. 2006 Mar;2(3):e38. DOI:10.1371/journal.pgen.0020038 |
6. Steinbacher S, Hof P, Eichinger L, Schleicher M, Gettemans J, Vandekerckhove J, Huber R, and Benz J. The crystal structure of the Physarum polycephalum actin-fragmin kinase: an atypical protein kinase with a specialized substrate-binding domain. EMBO J. 1999 Jun 1;18(11):2923-9. DOI:10.1093/emboj/18.11.2923 |