title: Multiple isoforms for the catalytic subunit of PKA in the basal fungal lineage Mucor circinelloides.
abstract: Protein kinase A (PKA) activity is involved in dimorphism of the basal fungal lineage Mucor. From the recently sequenced genome of Mucor circinelloides we could predict ten catalytic subunits of PKA. From sequence alignment and structural prediction we conclude that the catalytic core of the isoforms is conserved, and the difference between them resides in their amino termini. This high number of isoforms is maintained in the subdivision Mucoromycotina. Each paralogue, when compared to the ones form other fungi is more homologous to one of its orthologs than to its paralogs. All of these fungal isoforms cannot be included in the class I or II in which fungal protein kinases have been classified. mRNA levels for each isoform were measured during aerobic and anaerobic growth. The expression of each isoform is differential and associated to a particular growth stage. We reanalyzed the sequence of PKAC (GI 20218944), the only cloned sequence available until now for a catalytic subunit of M. circinelloides. PKAC cannot be classified as a PKA because of its difference in the conserved C-tail; it shares with PKB a conserved C2 domain in the N-terminus. No catalytic activity could be measured for this protein nor predicted bioinformatically. It can thus be classified as a pseudokinase. Its importance can not be underestimated since it is expressed at the mRNA level in different stages of growth, and its deletion is lethal.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Intendente Güiraldes 2160 - Ciudad Universitaria - C1428EGA, Buenos Aires, Argentina.
authors.forename: Lucas
authors.initials: L
authors.lastname: Fernández Núñez
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Intendente Güiraldes 2160 - Ciudad Universitaria - C1428EGA, Buenos Aires, Argentina.
authors.forename: Josefina
authors.initials: J
authors.lastname: Ocampo
authors.affiliation: Departamento de Ecologia, Genética y Evolución, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IEGEBA-CONICET, Intendente Güiraldes 2160 - Ciudad Universitaria - C1428EGA, Buenos Aires, Argentina.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Gottlieb
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Intendente Güiraldes 2160 - Ciudad Universitaria - C1428EGA, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Intendente Güiraldes 2160 - Ciudad Universitaria - C1428EGA, Buenos Aires, Argentina. Electronic address: smoreno@qb.fcen.uba.ar.
authors.forename: Silvia
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D020134:Catalytic Domain / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D020869:Gene Expression Profiling; D009089:Mucor / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017385:Sequence Homology
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Differentiation; Orthologs; Paralogs; Pseudokinase; Zygomycetes; cAMP