Multiple isoforms for the catalytic subunit of PKA in the basal fungal lineage Mucor circinelloides

FERNANDEZ NUÑEZ, LUCAS; OCAMPO, J; GOTTLIEB, ALEXANDRA; ROSSI, SILVIA; MORENO, SILVIA

Fungal Biology

Elsevier Editorial System

Año: 2016

3 Protein kinase A (PKA) activity is involved in dimorphism of the basal fungal lineage Mucor.4 From the recently sequenced genome of Mucor circinelloides we could predict ten catalytic5 subunits of PKA. From sequence alignment and structural prediction we conclude that the6 catalytic core of the isoforms is conserved, and the difference between them resides in their7 amino termini. This high numer of isoforms is maintained in the subdivision Mucoromycotina.8 Each paralogue, when compared to the ones form other fungi is more homologous to one of its9 orthologs than to its paralogs. All of these fungal isoforms cannot be included in the class I or II10 in which fungal protein kinases have been classified. mRNA levels for each isoform were11 measured during aerobic and anaerobic growth. The expression of each isoform is differential12 and associated to a particular growth stage. We reanalyzed the sequence of PKAC (GI13 20218944), the only cloned sequence available until now for a catalytic subunit of M.14 circinelloides. PKAC cannot be classified as a PKA because of its difference in the conserved C15tail; it shares with PKB a conserved C2 domain in the N-terminus. No catalytic activity could be16 measured for this protein nor predicted bioinformatically. It can thus be classified as a17 pseudokinase. Its importance can not be underestimated since it is expressed at the mRNA level18 in different stages of growth, and its deletion is lethal.