Virulence without catalysis: How can a pseudokinase affect host cell signaling?

Trends in Parasitology

Volumn 28, Issue 2, 2012, Pages 53-57

  Reese, Michael L ^a   Boyle, Jon P ^b  

^a STANFORD UNIVERSITY   (United States)

^b UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN KINASE; PSEUDOKINASE; UNCLASSIFIED DRUG;

CATALYSIS; COPY NUMBER VARIATION; DNA POLYMORPHISM; ENZYME ACTIVE SITE; GENE DOSAGE; GENE DUPLICATION; GENE FUNCTION; GENE LOCUS; GENE SEQUENCE; GENETIC VARIABILITY; HOST CELL; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; TOXOPLASMA GONDII; VIRULENCE;

CATALYSIS; HOST-PARASITE INTERACTIONS; HUMANS; MODELS, MOLECULAR; POLYMORPHISM, GENETIC; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; PROTOZOAN PROTEINS; SIGNAL TRANSDUCTION; TOXOPLASMA;

TOXOPLASMA; TOXOPLASMA GONDII;

EID: 84856236887     PISSN: 14714922     EISSN: 14715007     Source Type: Journal    
DOI: 10.1016/j.pt.2011.12.004     Document Type: Review

References (42)

1. Boothroyd J.C., Dubremetz J.-F. Kiss and spit: the dual roles of Toxoplasma rhoptries. Nat. Rev. Microbiol. 2008, 6:79-88.
2. Boudeau J., et al. Emerging roles of pseudokinases. Trends Cell Biol. 2006, 16:443-452.
3. Zeqiraj E., van Aalten D.M.F. Pseudokinases - remnants of evolution or key allosteric regulators?. Curr. Opin. Struct. Biol. 2010, 20:772-781.
4. Truitt L., Freywald A. Dancing with the dead: Eph receptors and their kinase-null partners. Biochem. Cell Biol. 2011, 89:115-129.
5. Saharinen P., Silvennoinen O. The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. J. Biol. Chem. 2002, 277:47954-47963.
6. Peixoto L., et al. Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses. Cell Host Microbe 2010, 8:208-218.
7. Reese M.L., et al. Polymorphic family of injected pseudokinases is paramount in Toxoplasma virulence. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:9625-9630.
8. Behnke M.S., et al. Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:9631-9636.
9. Beckers C.J., et al. The expression of Toxoplasma proteins in Neospora caninum and the identification of a gene encoding a novel rhoptry protein. Mol. Biochem. Parasitol. 1997, 89:209-223.
10. Zhang F., et al. Copy number variation in human health, disease, and evolution. Annu. Rev. Genomics Hum. Genet. 2009, 10:451-481.
11. Sudmant P.H., et al. Diversity of human copy number variation and multicopy genes. Science 2010, 330:641-646.
12. Andersson D.I., et al. Evidence that gene amplification underlies adaptive mutability of the bacterial lac operon. Science 1998, 282:1133-1135.
13. Cowman A.F., et al. Selection for mefloquine resistance in Plasmodium falciparum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:1143-1147.
14. Paton M.G., et al. Quantitative analysis of gene amplification in insecticide-resistant Culex mosquitoes. Biochem. J. 2000, 346:17-24.
15. Bergthorsson U., et al. Ohno's dilemma: evolution of new genes under continuous selection. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:17004-17009.
16. Bridgham J.T., et al. Evolution of a new function by degenerative mutation in cephalochordate steroid receptors. PLoS Genet. 2008, 4:e1000191.
17. Sawyer S.L., et al. Discordant evolution of the adjacent antiretroviral genes TRIM22 and TRIM5 in mammals. PLoS Pathog. 2007, 3:e197.
18. Hunn J.P., et al. The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens. Mamm. Genome 2011, 22:43-54.
19. Saeij J.P.J., et al. Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 2006, 314:1780-1783.
20. Su C., et al. Recent expansion of Toxoplasma through enhanced oral transmission. Science 2003, 299:414-416.
21. Labesse G., et al. ROP2 from Toxoplasma gondii: a virulence factor with a protein-kinase fold and no enzymatic activity. Structure 2009, 17:139-146.
22. Qiu W., et al. Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii. EMBO J. 2009, 28:969-979.
23. Reese M.L., Boothroyd J.C. A conserved non-canonical motif in the pseudoactive site of the ROP5 pseudokinase domain mediates its effect on Toxoplasma virulence. J. Biol. Chem. 2011, 286:29366-29375.
24. Pawson T., et al. SH2 domains, interaction modules and cellular wiring. Trends Cell Biol. 2001, 11:504-511.
25. Harris B.Z., Lim W.A. Mechanism and role of PDZ domains in signaling complex assembly. J. Cell Sci. 2001, 114:3219-3231.
26. Nagar B., et al. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 2003, 112:859-871.
27. Kannan N., et al. 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, 104:1272-1277.
28. Fischmann T.O., et al. Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors. Biochemistry 2009, 48:2661-2674.
29. Brennan D.F., et al. A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK. Nature 2011, 472:366-369.
30. Soo V.W.C., et al. Artificial gene amplification reveals an abundance of promiscuous resistance determinants in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:1484-1489.
31. Lingelbach K., Przyborski J.M. The long and winding road: protein trafficking mechanisms in the Plasmodium falciparum infected erythrocyte. Mol. Biochem. Parasitol. 2006, 147:1-8.
32. Elde N.C., et al. Protein kinase R reveals an evolutionary model for defeating viral mimicry. Nature 2009, 457:485-489.
33. Rothenburg S., et al. Rapid evolution of protein kinase PKR alters sensitivity to viral inhibitors. Nat. Struct. Mol. Biol. 2009, 16:63-70.
34. Zeqiraj E., et al. Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation. Science 2009, 326:1707-1711.
35. Zeqiraj E., et al. ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor. PLoS Biol. 2009, 7:e1000126.
36. Fukuda K., et al. The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions. Mol. Cell 2009, 36:819-830.
37. Hu J., et al. Mutation that blocks ATP binding creates a pseudokinase stabilizing the scaffolding function of kinase suppressor of Ras, CRAF and BRAF. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:6067-6072.
38. Won A.P., et al. Recruitment interactions can override catalytic interactions in determining the functional identity of a protein kinase. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:9809-9814.
39. Saeij J.P.J., et al. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 2007, 445:324-327.
40. Taylor S., et al. A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 2006, 314:1776-1780.
41. Gilbert L.A., et al. Toxoplasma gondii targets a protein phosphatase 2C to the nuclei of infected host cells. Eukaryot. Cell 2007, 6:73-83.
42. Hanks S.K., Hunter T. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J. 1995, 9:576-596.