title: Proteomic analysis of the signaling pathway mediated by the heterotrimeric Gα protein Pga1 of Penicillium chrysogenum.
abstract: BACKGROUND
  The heterotrimeric Gα protein Pga1-mediated signaling pathway regulates the entire developmental program in Penicillium chrysogenum, from spore germination to the formation of conidia. In addition it participates in the regulation of penicillin biosynthesis. We aimed to advance the understanding of this key signaling pathway using a proteomics approach, a powerful tool to identify effectors participating in signal transduction pathways.
  
  
  RESULTS
  Penicillium chrysogenum mutants with different levels of activity of the Pga1-mediated signaling pathway were used to perform comparative proteomic analyses by 2D-DIGE and LC-MS/MS. Thirty proteins were identified which showed differences in abundance dependent on Pga1 activity level. By modifying the intracellular levels of cAMP we could establish cAMP-dependent and cAMP-independent pathways in Pga1-mediated signaling. Pga1 was shown to regulate abundance of enzymes in primary metabolic pathways involved in ATP, NADPH and cysteine biosynthesis, compounds that are needed for high levels of penicillin production. An in vivo phosphorylated protein containing a pleckstrin homology domain was identified; this protein is a candidate for signal transduction activity. Proteins with possible roles in purine metabolism, protein folding, stress response and morphogenesis were also identified whose abundance was regulated by Pga1 signaling.
  
  
  CONCLUSIONS
  Thirty proteins whose abundance was regulated by the Pga1-mediated signaling pathway were identified. These proteins are involved in primary metabolism, stress response, development and signal transduction. A model describing the pathways through which Pga1 signaling regulates different cellular processes is proposed.
authors.affiliation: Departamento de Biotecnología, Universidad Autónoma Metropolitana-Unidad Iztapalapa, México D.F., México.
authors.forename: Ulises
authors.initials: U
authors.lastname: Carrasco-Navarro
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
authors.forename: Rosario
authors.initials: R
authors.lastname: Vera-Estrella
authors.affiliation: Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia.
authors.forename: Bronwyn J
authors.initials: BJ
authors.lastname: Barkla
authors.affiliation: Departamento de Biotecnología, Universidad Autónoma Metropolitana-Unidad Iztapalapa, México D.F., México.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Zúñiga-León
authors.affiliation: Laboratorio de Bioquímica-Genética, Instituto Nacional de Pediatría, Secretaría de Salud, México D.F., México.
authors.forename: Horacio
authors.initials: H
authors.lastname: Reyes-Vivas
authors.affiliation: Departamento de Biotecnología, Universidad Autónoma Metropolitana-Unidad Iztapalapa, México D.F., México.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Fernández
authors.affiliation: Departamento de Biotecnología, Universidad Autónoma Metropolitana-Unidad Iztapalapa, México D.F., México. fierrof@xanum.uam.mx.
authors.forename: Francisco
authors.identifier: http://orcid.org/0000-0002-2582-5362
authors.initials: F
authors.lastname: Fierro
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D009024:Morphogenesis; D009154:Mutation; D010085:Oxidative Phosphorylation; D010408:Penicillium chrysogenum / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000070539:Pleckstrin Homology Domains; D040901:Proteomics; D011687:Purines / Q000378:metabolism; D015398:Signal Transduction; D013172:Spores, Fungal / Q000254:growth & development; D053719:Tandem Mass Spectrometry; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D005656:Fungal Proteins; D044385:GTP-Binding Protein alpha Subunits; D011687:Purines
keywords: Heterotrimeric G protein; Penicillin biosynthesis; Penicillium chrysogenum; Pga1 Gα subunit; Proteomics; Signal transduction