1887

Abstract

The G5 subunit has been shown to reduce cell viability, inhibit folate chemotaxis and accelerate tip morphogenesis and gene expression during multicellular development. Alteration of the D-motif (mitogen-activated protein kinase docking site) at the amino terminus of the G5 subunit or the loss of extracellular signal-regulated kinase (ERK)1 diminished the lethality associated with the overexpression or constitutive activation of the G5 subunit. The amino-terminal D-motif of the G5 subunit was also found to be necessary for the reduced cell size, small aggregate formation and precocious developmental gene expression associated with G5 subunit overexpression. This D-motif also contributed to the aggregation delay in cells expressing a constitutively active G5 subunit, but the D-motif was not necessary for the inhibition of folate chemotaxis. These results suggest that the amino-terminal D-motif is required for some but not all phenotypes associated with elevated G5 subunit functions during growth and development and that ERK1 can function in G5 subunit-mediated signal transduction.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.036541-0
2010-03-01
2019-10-14
Loading full text...

Full text loading...

/deliver/fulltext/micro/156/3/789.html?itemId=/content/journal/micro/10.1099/mic.0.036541-0&mimeType=html&fmt=ahah

References

  1. Albert, P. R. & Robillard, L. ( 2002; ). G protein specificity: traffic direction required. Cell Signal 14, 407–418.[CrossRef]
    [Google Scholar]
  2. Arnold, K., Bordoli, L., Kopp, J. & Schwede, T. ( 2006; ). The swiss-model workspace:a web-based environment for protein structure homology modelling. Bioinformatics 22, 195–201.[CrossRef]
    [Google Scholar]
  3. Aubry, L. & Firtel, R. ( 1999; ). Integrationof signaling networks that regulate Dictyostelium differentiation. Annu Rev Cell Dev Biol 15, 469–517.[CrossRef]
    [Google Scholar]
  4. Blackwell, E., Halatek, I. M., Kim, H. J., Ellicott, A. T.,Obukhov, A. A. & Stone, D. E. ( 2003; ). Effect ofthe pheromone-responsive G(alpha) and phosphatase proteins of Saccharomyces cerevisiae on the subcellular localization of the Fus3mitogen-activated protein kinase. Mol Cell Biol 23, 1135–1150.[CrossRef]
    [Google Scholar]
  5. Bradford, M. M. ( 1976; ). A rapid andsensitive method for the quantitation of microgram quantities of protein utilizingthe principle of protein-dye binding. Anal Biochem 72, 248–254.[CrossRef]
    [Google Scholar]
  6. Brzostowski, J. A. & Kimmel, A. R. ( 2006; ). Nonadaptive regulation of ERK2 in Dictyostelium: implications for mechanismsof cAMP relay. Mol Biol Cell 17, 4220–4227.[CrossRef]
    [Google Scholar]
  7. Caunt, C. J., Finch, A. R., Sedgley, K. R. & McArdle, C.A. ( 2006; ). Seven-transmembrane receptor signallingand ERK compartmentalization. Trends Endocrinol Metab 17, 276–283.[CrossRef]
    [Google Scholar]
  8. Feinberg, A. P. & Vogelstein, B. ( 1983; ). A technique for radiolabeling DNA restriction endonuclease fragmentsto high specific activity. Anal Biochem 132, 6–13.[CrossRef]
    [Google Scholar]
  9. Firtel, R. A. ( 1996; ). Interacting signalingpathways controlling multicellular development in Dictyostelium. Curr Opin Genet Dev 6, 545–554.[CrossRef]
    [Google Scholar]
  10. Firtel, R. A., van Haastert, P. J., Kimmel, A. R. & Devreotes,P. N. ( 1989; ). G protein linked signal transductionpathways in development: Dictyostelium as an experimental system. Cell 58, 235–239.[CrossRef]
    [Google Scholar]
  11. Gaskins, C., Maeda, M. & Firtel, R. A. ( 1994; ). Identification and functional analysis of a developmentallyregulated extracellular signal-regulated kinase gene in Dictyosteliumdiscoideum. Mol Cell Biol 14, 6996–7012.
    [Google Scholar]
  12. Goldberg, J. M., Manning, G., Liu, A., Fey, P., Pilcher, K.E., Xu, Y. & Smith, J. L. ( 2006; ). The dictyosteliumkinome – analysis of the protein kinases from a simple model organism. PLoS Genet 2, e38 [CrossRef]
    [Google Scholar]
  13. Grewal, S., Molina, D. M. & Bardwell, L. ( 2006; ). Mitogen-activated protein kinase (MAPK)-dockingsites in MAPK kinases function as tethers that are crucial for MAPK regulation in vivo. Cell Signal 18, 123–134.[CrossRef]
    [Google Scholar]
  14. Hadwiger, J. A. ( 2007; ). Developmentalmorphology and chemotactic responses are dependent on G alpha subunit specificityin Dictyostelium. Dev Biol 312, 1–12.[CrossRef]
    [Google Scholar]
  15. Hadwiger, J. A., Natarajan, K. & Firtel, R. A. ( 1996; ). Mutations in the Dictyostelium heterotrimeric Gprotein α subunit Gα5 alter the kinetics of tipmorphogenesis. Development 122, 1215–1224.
    [Google Scholar]
  16. Hildebrandt, J. D. ( 1997; ). Role of subunitdiversity in signaling by heterotrimeric G proteins. Biochem Pharmacol 54, 325–339.[CrossRef]
    [Google Scholar]
  17. Holbrook, S. R. & Kim, S. H. ( 1989; ). Molecular model of the G protein alpha subunit based on the crystal structureof the HRAS protein. Proc Natl Acad Sci U S A 86, 1751–1755.[CrossRef]
    [Google Scholar]
  18. Hopper, N. A., Sanders, G. M., Fosnaugh, K. L., Williams, J.G. & Loomis, W. F. ( 1995; ). Protein kinase A isa positive regulator of spore coat gene transcription in Dictyostelium. Differentiation 58, 183–188.[CrossRef]
    [Google Scholar]
  19. Hur, E. M. & Kim, K. T. ( 2002; ).G protein-coupled receptor signalling and cross-talk: achieving rapidity andspecificity. Cell Signal 14, 397–405.[CrossRef]
    [Google Scholar]
  20. Knetsch, M. L., Epskamp, S. J., Schenk, P. W., Wang, Y., Segall,J. E. & Snaar-Jagalska, B. E. ( 1996; ). Dual roleof cAMP and involvement of both G-proteins and ras in regulation of ERK2 in Dictyostelium discoideum. EMBO J 15, 3361–3368.
    [Google Scholar]
  21. Landry, Y. & Gies, J. P. ( 2002; ).Heterotrimeric G proteins control diverse pathways of transmembrane signaling,a base for drug discovery. Mini Rev Med Chem 2, 361–372.[CrossRef]
    [Google Scholar]
  22. Levi, S., Polyakov, M. & Egelhoff, T. T. ( 2000; ). Green fluorescent protein and epitope tag fusion vectorsfor Dictyostelium discoideum. Plasmid 44, 231–238.[CrossRef]
    [Google Scholar]
  23. Maeda, M. & Firtel, R. A. ( 1997; ).Activation of the mitogen-activated protein kinase ERK2 by the chemoattractantfolic acid in Dictyostelium. J Biol Chem 272, 23690–23695.[CrossRef]
    [Google Scholar]
  24. Maeda, M., Aubry, L., Insall, R., Gaskins, C., Devreotes, P.N. & Firtel, R. A. ( 1996; ). Seven helix chemoattractantreceptors transiently stimulate mitogen-activated protein kinase in Dictyostelium – role of heterotrimeric G proteins. J Biol Chem 271, 3351–3354.[CrossRef]
    [Google Scholar]
  25. Maeda, M., Lu, S., Shaulsky, G., Miyazaki, Y., Kuwayama, H.,Tanaka, Y., Kuspa, A. & Loomis, W. F. ( 2004; ).Periodic signaling controlled by an oscillatory circuit that includes proteinkinases ERK2 and PKA. Science 304, 875–878.[CrossRef]
    [Google Scholar]
  26. Mann, S. K. & Firtel, R. A. ( 1993; ). cAMP-dependent protein kinase differentially regulates prestalk and presporedifferentiation during Dictyostelium development. Development 119, 135–146.
    [Google Scholar]
  27. Mann, S. K., Richardson, D. L., Lee, S., Kimmel, A. R. &Firtel, R. A. ( 1994; ). Expression of cAMP-dependentprotein kinase in prespore cells is sufficient to induce spore cell differentiationin Dictyostelium. Proc Natl Acad Sci U S A 91, 10561–10565.[CrossRef]
    [Google Scholar]
  28. Metodiev, M. V., Matheos, D., Rose, M. D. & Stone, D. E. ( 2002; ). Regulation of MAPK function by direct interactionwith the mating-specific Gα in yeast. Science 296, 1483–1486.[CrossRef]
    [Google Scholar]
  29. Milligan, G. & Kostenis, E. ( 2006; ). Heterotrimeric G-proteins: a short history. Br J Pharmacol 147, (Suppl. 1), S46–S55.
    [Google Scholar]
  30. Miranda-Saavedra, D. & Barton, G. J. ( 2007; ). Classification and functional annotation of eukaryotic proteinkinases. Proteins 68, 893–914.[CrossRef]
    [Google Scholar]
  31. Natarajan, K., Ashley, C. A. & Hadwiger, J. A. ( 2000; ). Related Gα subunits play opposing roles during Dictyostelium development. Differentiation 66, 136–146.[CrossRef]
    [Google Scholar]
  32. Neves, S. R., Ram, P. T. & Iyengar, R. ( 2002; ). G protein pathways. Science 296, 1636–1639.[CrossRef]
    [Google Scholar]
  33. Nguyen, H. N. & Hadwiger, J. A. ( 2009; ). The Gα4 G protein subunit interacts with the MAP kinaseERK2 using a D-motif that regulates developmental morphogenesis in Dictyostelium. Dev Biol 335, 385–395.[CrossRef]
    [Google Scholar]
  34. Nguyen, H.-N., Raisley, B. & Hadwiger, J. A. ( 2010; ). MAP Kinases have different functions in Dictyostelium G Protein-Mediated Signaling. Cell Signal (inpress). doi:10.1016/j.cellsig.2010.01.008.
    [Google Scholar]
  35. Offermanns, S. & Simon, M. I. ( 1998; ). Genetic analysis of mammalian G-protein signalling. Oncogene 17, 1375–1381.[CrossRef]
    [Google Scholar]
  36. Raman, M., Chen, W. & Cobb, M. H. ( 2007; ). Differential regulation and properties of MAPKs. Oncogene 26, 3100–3112.[CrossRef]
    [Google Scholar]
  37. Remenyi, A., Good, M. C., Bhattacharyya, R. P. & Lim, W.A. ( 2005; ). The role of docking interactions in mediatingsignaling input, output, and discrimination in the yeast MAPK network. Mol Cell 20, 951–962.[CrossRef]
    [Google Scholar]
  38. Segall, J. E., Kuspa, A., Shaulsky, G., Ecke, M., Maeda, M.,Gaskins, C., Firtel, R. A. & Loomis, W. F. ( 1995; ). A MAP kinase necessary for receptor-mediated activation of adenylyl cyclasein Dictyostelium. J Cell Biol 128, 405–413.[CrossRef]
    [Google Scholar]
  39. Simon, M. I., Strathmann, M. P. & Gautam, N. ( 1991; ). Diversity of G proteins in signal transduction. Science 252, 802–808.[CrossRef]
    [Google Scholar]
  40. Sobko, A., Ma, H. & Firtel, R. A. ( 2002; ). Regulated SUMOylation and ubiquitination of DdMEK1 is required for properchemotaxis. Dev Cell 2, 745–756.[CrossRef]
    [Google Scholar]
  41. Srinivasan, J., Gundersen, R. E. & Hadwiger, J. A. ( 1999; ). Activated Gα subunits can inhibit multiplesignal transduction pathways during dictyostelium development. Dev Biol 215, 443–452.[CrossRef]
    [Google Scholar]
  42. Watts, D. J. & Ashworth, J. M. ( 1970; ). Growth of myxameobae of the cellular slime mould Dictyostelium discoideum in axenic culture. Biochem J 119, 171–174.
    [Google Scholar]
  43. Wilkie, T. M., Gilbert, D. J., Olsen, A. S., Chen, X. N., Amatruda,T. T., Korenberg, J. R., Trask, B. J., de Jong, P., Reed, R. R. & otherauthors ( 1992; ). Evolution of the mammalian G proteinalpha subunit multigene family. Nat Genet 1, 85–91.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.036541-0
Loading
/content/journal/micro/10.1099/mic.0.036541-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error