Tarique Sarwar, Abdul Rouf Banday, Mohammad Tabish
Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, 202002, India.
PKA (Protein Kinase-A) is a second messenger-dependent enzyme that has been implicated in a wide range of cellular processes, including transcription, metabolism, cell cycle progression and apoptosis. The known modulators of PKA activity include factors that either activate or inhibit Adenylate Cyclase, resulting in an increase or decrease in cAMP levels. The enzyme occurs naturally as a four-membered structure with two regulatory (R) and two catalytic (C) subunits. There are two major genes in mammals including mouse that encode for catalytic subunits catalytic alpha (Cα) and catalytic beta (Cβ) of PKA. The murine, bovine and human Cβ genes encode several splice variants. In humans ten splice variants namely Cβ1, Cβ2, Cβ3, Cβ3b, Cβ3ab, Cβ3abc, Cβ4, Cβ4b, Cβ4ab and Cβ4abc have been reported so far. The four murine Cβ gene splice variants are homologues of Cβ1, Cβ2, Cβ3 and Cβ4 of humans. Using combinatorial approach of bioinformatics tools and molecular biology techniques, we have identified eight novel splice variants of mouse Cβ gene (Prkacb) that have different 5′ coding exons. The new variants were designated as Cβ5, Cβ6, Cβ6b, Cβ7, Cβ7b, Cβ7ab, Cβ7abc and Cβ8. These new variants showed differential pattern of expression in tissue and developmental stage specific manner. The Cβ5, Cβ6 and Cβ8 are expressed in brain, liver, heart and skeletal muscle but all other are tissue specific such as Cβ6b is expressed in heart; Cβ7 is expressed in adult mouse muscle; Cβ7b is expressed in adult mouse liver; Cβ7ab is expressed in three day old mouse brain and Cβ7abc is expressed in three day old mouse muscle. The posttranslational modification prediction using Expasy tools showed characteristic signature sequences in predicted proteins important for functionality of protein. This study clearly showed that Prkacb gene of mouse undergoes extensive alternative splicing in 5′ region producing tissue and developmental stage specific variants deferring at N-terminals. Read More …