Abstract
Phosphorylase kinase (PhK) is a 1.3 x 106 Da serine-threonine protein kinase that plays an important role in glycogen breakdown. PhK is a hexadecamer of 4 subunits with (αβγδ)4 stoichiometry. The γ subunit is the catalytic subunit of the holoenzyme and contains a kinase domain and a C-terminal calmodulin binding domain. Two tissue-specific isoforms of γ exist, muscle and liver, each encoded by separate genes, PHKG1 and PHKG2 respectively. To identify potential regulatory mechanism that mediate the temporal expression of PHKG2 gene, the putative human promoter region was analyzed. Sequence comparison reveals that the PHKG2 promoter shares 42% identity with PHKG1. Additionally, evolutionary comparisons reveal 46% and 46% sequence conservation of the human PHKG2 promoter to rat and mouse respectively. Based upon TransFac Analysis several putative transcription factor binding domains were identified that may regulate liver-specific expression: 1 hepatic nuclear factor (HNF) 3β, 1 HNF-4, and 4 activator protein (AP) 1 sites. Biochemical analysis of this promoter has been performed in muscle-specific (C2C12) and liver-specific (HepG2) cells. The information obtained from this study will further advance our understanding of the various glycogenoses that result from mutations in the PHKG2 gene. Support of the National Institutes of Health and the National Center for Research Resources Grant P2ORR16481 is gratefully acknowledged.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call