Logo of iaiPermissionsJournals.ASM.orgJournalIAI ArticleJournal InfoAuthorsReviewers
Infect Immun. 1996 Mar; 64(3): 691–701.
PMCID: PMC173824

Signal transduction in Pneumocystis carinii: characterization of the genes (pcg1) encoding the alpha subunit of the G protein (PCG1) of Pneumocystis carinii carinii and Pneumocystis carinii ratti.


Pneumocystis carinii is a eukaryotic organism that causes pneumonia in immunocompromised hosts. The cell biology and life cycle of the organism are poorly understood primarily because of the lack of a continuous in vitro cultivation system. These limitations have prevented investigation of the organism's infectious cycle and hindered the rational development of new antimicrobial therapies and implementation of measures to prevent exposure to the organism or transmission. The interaction of P. carinii with its host and its environment may be critical determinants of pathogenicity and life cycle. Signal transduction pathways are likely to be critical in regulating these processes. G proteins are highly conserved members of the pathways important in many cellular events, including cell proliferation and environmental sensing. To characterize signal transduction pathways in P. carinii, we cloned a G-protein alpha subunit (G-alpha) of P. carinii carinii and P. carinii ratti by PCR amplification and hybridization screening. The gene encoding the G-alpha was present in single copy on a 450-kb chromosome of P.c. ratti. The 1,062-bp G-alpha open reading frame is interrupted by nine introns. The predicted polypeptide showed 29 to 53% identity with known fungal G-alpha proteins with greatest homology to Neurospora crassa Gna-2. Northern (RNA) blot analysis and immunoprecipitation demonstrated expression of the G-alpha mRNA and protein P. carinii isolated from heavily infected animals. Some alteration in the level of transcription was noted in short-term maintenance in starvation or rich medium. Characterization of signal transduction in P. carinii will permit a better understanding of the reproductive capacity and other cellular processes in this family or organisms that cannot be cultured continuously.

Full Text

The Full Text of this article is available as a PDF (555K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Chen F, Cushion MT. Use of an ATP bioluminescent assay to evaluate viability of Pneumocystis carinii from rats. J Clin Microbiol. 1994 Nov;32(11):2791–2800. [PMC free article] [PubMed]
  • Choi GH, Chen B, Nuss DL. Virus-mediated or transgenic suppression of a G-protein alpha subunit and attenuation of fungal virulence. Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):305–309. [PMC free article] [PubMed]
  • Cushion MT, Kaselis M, Stringer SL, Stringer JR. Genetic stability and diversity of Pneumocystis carinii infecting rat colonies. Infect Immun. 1993 Nov;61(11):4801–4813. [PMC free article] [PubMed]
  • Cushion MT, Zhang J, Kaselis M, Giuntoli D, Stringer SL, Stringer JR. Evidence for two genetic variants of Pneumocystis carinii coinfecting laboratory rats. J Clin Microbiol. 1993 May;31(5):1217–1223. [PMC free article] [PubMed]
  • Dietzel C, Kurjan J. The yeast SCG1 gene: a G alpha-like protein implicated in the a- and alpha-factor response pathway. Cell. 1987 Sep 25;50(7):1001–1010. [PubMed]
  • Dohlman HG, Goldsmith P, Spiegel AM, Thorner J. Pheromone action regulates G-protein alpha-subunit myristoylation in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9688–9692. [PMC free article] [PubMed]
  • Edman U, Edman JC, Lundgren B, Santi DV. Isolation and expression of the Pneumocystis carinii thymidylate synthase gene. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6503–6507. [PMC free article] [PubMed]
  • Isshiki T, Mochizuki N, Maeda T, Yamamoto M. Characterization of a fission yeast gene, gpa2, that encodes a G alpha subunit involved in the monitoring of nutrition. Genes Dev. 1992 Dec;6(12B):2455–2462. [PubMed]
  • Kozak M. Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Microbiol Rev. 1983 Mar;47(1):1–45. [PMC free article] [PubMed]
  • Kurjan J. The pheromone response pathway in Saccharomyces cerevisiae. Annu Rev Genet. 1993;27:147–179. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Miyajima I, Nakafuku M, Nakayama N, Brenner C, Miyajima A, Kaibuchi K, Arai K, Kaziro Y, Matsumoto K. GPA1, a haploid-specific essential gene, encodes a yeast homolog of mammalian G protein which may be involved in mating factor signal transduction. Cell. 1987 Sep 25;50(7):1011–1019. [PubMed]
  • Nakafuku M, Itoh H, Nakamura S, Kaziro Y. Occurrence in Saccharomyces cerevisiae of a gene homologous to the cDNA coding for the alpha subunit of mammalian G proteins. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2140–2144. [PMC free article] [PubMed]
  • Nakafuku M, Obara T, Kaibuchi K, Miyajima I, Miyajima A, Itoh H, Nakamura S, Arai K, Matsumoto K, Kaziro Y. Isolation of a second yeast Saccharomyces cerevisiae gene (GPA2) coding for guanine nucleotide-binding regulatory protein: studies on its structure and possible functions. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1374–1378. [PMC free article] [PubMed]
  • Neer EJ. Heterotrimeric G proteins: organizers of transmembrane signals. Cell. 1995 Jan 27;80(2):249–257. [PubMed]
  • Neiman AM, Stevenson BJ, Xu HP, Sprague GF, Jr, Herskowitz I, Wigler M, Marcus S. Functional homology of protein kinases required for sexual differentiation in Schizosaccharomyces pombe and Saccharomyces cerevisiae suggests a conserved signal transduction module in eukaryotic organisms. Mol Biol Cell. 1993 Jan;4(1):107–120. [PMC free article] [PubMed]
  • Obara T, Nakafuku M, Yamamoto M, Kaziro Y. Isolation and characterization of a gene encoding a G-protein alpha subunit from Schizosaccharomyces pombe: involvement in mating and sporulation pathways. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5877–5881. [PMC free article] [PubMed]
  • Sadhu C, Hoekstra D, McEachern MJ, Reed SI, Hicks JB. A G-protein alpha subunit from asexual Candida albicans functions in the mating signal transduction pathway of Saccharomyces cerevisiae and is regulated by the a1-alpha 2 repressor. Mol Cell Biol. 1992 May;12(5):1977–1985. [PMC free article] [PubMed]
  • Sunkin SM, Stringer JR. Transcription factor genes from rat Pneumocystis carinii. J Eukaryot Microbiol. 1995 Jan-Feb;42(1):12–19. [PubMed]
  • Tolkacheva T, McNamara P, Piekarz E, Courchesne W. Cloning of a Cryptococcus neoformans gene, GPA1, encoding a G-protein alpha-subunit homolog. Infect Immun. 1994 Jul;62(7):2849–2856. [PMC free article] [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Turner GE, Borkovich KA. Identification of a G protein alpha subunit from Neurospora crassa that is a member of the Gi family. J Biol Chem. 1993 Jul 15;268(20):14805–14811. [PubMed]
  • Vasquez J, Smulian AG, Linke MJ, Cushion MT. Antigenic differences among genetically distinct types of rat-derived Pneumocystis carinii. J Eukaryot Microbiol. 1994 Sep-Oct;41(5):114S–114S. [PubMed]
  • Walzer PD, Linke MJ. A comparison of the antigenic characteristics of rat and human Pneumocystis carinii by immunoblotting. J Immunol. 1987 Apr 1;138(7):2257–2265. [PubMed]
  • Weinberg GA, O'Gara MJ, Cushion MT. Coinfection of rats with genetically diverse forms of Pneumocystis carinii demonstrated by P. carinii inosine monophosphate dehydrogenase gene polymorphism. J Eukaryot Microbiol. 1994 Sep-Oct;41(5):119S–119S. [PubMed]
  • Wilkie TM, Yokoyama S. Evolution of the G protein alpha subunit multigene family. Soc Gen Physiol Ser. 1994;49:249–270. [PubMed]
  • Zhang J, Stringer JR. Cloning and characterization of an alpha-tubulin-encoding gene from rat-derived Pneumocystis carinii. Gene. 1993 Jan 15;123(1):137–141. [PubMed]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...