Characterization of a role for inositol polyphosphate multikinase in the regulation of serum response factor

Abstract

Inositol polyphosphate multikinase(IPMK), which is the key enzyme for the phosphatidylinositol 3,4,5-trisphosphate and biosynthesis of higher polyphosphates, also regulate multiple transcriptional factor in the nucleus. To elucidate mechanism how IPMK regulate SRF, purified SRF were labeled with fluorophores to detect dynamics when in the presence or absence of IPMK in single-molecule level. IPMK increased binding population and time of SRF to its target DNA sequence by inducing conformational change. To further prove function of IPMK is still valid in SRF as regulator of cell motility and expand this result to physiological level, K/BxN serum transfer arthritis model was conducted in myeloid cell-specific IPMK knock out mouse. In myeloid cell-specific IPMK knock out mouse, resolution of inflammation was delayed. To elaborate this phenotype, Fc receptor signaling, osteoclast differentiation and resolving D1 signaling was tested, but no difference was observed between wild type mouse and myeloid cell-specific IPMK knock out mouse. However, I proposed potential of IPMK as a repressor of rheumatoid arthritis.