Kinase Family PSK

Kinase Classification: Group CAMK: Family PSK

PSK is a CAMK kinase of obscure function.

Evolution

PSK is found in holozoans (animals+choanoflagellates). It is lost from Drosophila and all other insects. A mammalian-specific duplication gives rise to human PSKH1 and PSKH2. PSKH2 is lost in several lineages and shown to have lost a critical catalytic residue and catalytic function in primates [1, 2].

Domain Structure

PSKs have an N-terminal myristoylation signal embedded in a short conserved domain, followed by another conserved motif and a CAMK-group kinase domain.

Functions

PSK is poorly studied, with no homolog in Drosophila, and an uncharacterized homolog in C. elegans. Human PSKH1 is targeted to the Golgi apparatus and plasma membrane by its myristoylation on Gly2 and palmitoylation on Cys3, and expression of mutant PSKH1 could disassemble the Golgi apparatus [3]. PSKH1 has also been seen in the nucleus and centrosomes [4], and is associated with the splice factor compartment [5].

No substrates are known, but PSHK1 was shown to autophosphorylate on its C-terminal region [4].

In colon cancer cell lines, PSKH1 is a target of miR-566, a pro-survival, pro-proliferation miRNA [6]. PSKH1 was found as one of six kinases whose knockdown in prostate cancer cells inhibited growth [7]

High-throughput studies show that human PSKH1 interacts with several mitochondrial ribosomal proteins [8], and a smaller number of cytoplastmic ribosomal proteins, while PSKH2 was also shown to interact with mitochondrial proteins [2].

References

1. Caenepeel S, Charydczak G, Sudarsanam S, Hunter T, and Manning G. The mouse kinome: discovery and comparative genomics of all mouse protein kinases. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11707-12. DOI:10.1073/pnas.0306880101 |
2. Byrne DP, Shrestha S, Daly LA, Marensi V, Ramakrishnan K, Eyers CE, Kannan N, and Eyers PA. Evolutionary and cellular analysis of the 'dark' pseudokinase PSKH2. Biochem J. 2023 Jan 31;480(2):141-160. DOI:10.1042/BCJ20220474 |
3. Brede G, Solheim J, Stang E, and Prydz H. Mutants of the protein serine kinase PSKH1 disassemble the Golgi apparatus. Exp Cell Res. 2003 Dec 10;291(2):299-312. DOI:10.1016/j.yexcr.2003.07.009 |
4. Brede G, Solheim J, Tröen G, and Prydz H. Characterization of PSKH1, a novel human protein serine kinase with centrosomal, golgi, and nuclear localization. Genomics. 2000 Nov 15;70(1):82-92. DOI:10.1006/geno.2000.6365 |
4. Brede G, Solheim J, and Prydz H. PSKH1, a novel splice factor compartment-associated serine kinase. Nucleic Acids Res. 2002 Dec 1;30(23):5301-9. DOI:10.1093/nar/gkf648 |
6. Zhang Y, Zhang S, Yin J, and Xu R. MiR-566 mediates cell migration and invasion in colon cancer cells by direct targeting of PSKH1. Cancer Cell Int. 2019;19:333. DOI:10.1186/s12935-019-1053-1 |
7. Whitworth H, Bhadel S, Ivey M, Conaway M, Spencer A, Hernan R, Holemon H, and Gioeli D. Identification of kinases regulating prostate cancer cell growth using an RNAi phenotypic screen. PLoS One. 2012;7(6):e38950. DOI:10.1371/journal.pone.0038950 |
8. Buljan M, Ciuffa R, van Drogen A, Vichalkovski A, Mehnert M, Rosenberger G, Lee S, Varjosalo M, Pernas LE, Spegg V, Snijder B, Aebersold R, and Gstaiger M. Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Mol Cell. 2020 Aug 6;79(3):504-520.e9. DOI:10.1016/j.molcel.2020.07.001 |