Differentially expressed novel alternatively spliced transcript variant of tumor suppressor Stk11 gene in mouse

Serine/threonine kinase 11 (STK11) is a protein kinase that is encoded by Stk11 gene located on chromosome 19 and 10 in humans and mouse respectively. It acts as a master kinase of adenine monophosphate-activated protein kinase (AMPK) pathway that coordinates the regulation of cellular energy metabolism and cell division. STK11 exerts effect by activating more than 14 kinases including AMPK and AMPK-related kinases. It is also known to regulate cell polarity and acts as tumor suppressor. Alternative splicing of pre-mRNA is a mechanism which results in multiple transcript variants of a single gene. In human, two STK11 isoforms have been reported, an alternatively spliced isoform which has variation at its C-terminal and mostly expressed in testis (LKB1_S). Another isoform exhibiting oncogenic properties lacks few residues at its N-terminal (ΔN-LKB1). In the present study, we report the identification of a new transcript variant Stk11N which is generated through alternative splicing. The new variant was found to have differential and tissue specific expression at Postnatal-7 and adult stages of mouse. As compared to the known variant Stk11C, the conceptually translated amino acid sequences of the new variant differ from exon-E2 onwards. In silico post translational studies of the new and published variant show similarity in some of the properties while differ in properties like nuclear export signals, phosphorylation, glycosylation, etc. Thus, alternative splicing of Stk11 gene generating new variant with heterogeneous properties suggests for complex regulation of these variants in controlling the AMPK pathway and other functions.