Differential kinase activity of ACVR1 G328V and R206H mutations with implications to possible TβRI cross-talk in diffuse intrinsic pontine glioma.

ABSTRACT: Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain cancer whose median survival time is under one year. The possible roles of the two most common DIPG associated cytoplasmic ACVR1 receptor kinase domain mutants, G328V and R206H, are reexamined in the context of new biochemical results regarding their intrinsic relative ATPase activities. At 37 °C, the G328V mutant displays a 1.8-fold increase in intrinsic kinase activity over wild-type, whereas the R206H mutant shows similar activity. The higher G328V mutant intrinsic kinase activity is consistent with the statistically significant longer overall survival times of DIPG patients harboring ACVR1 G328V tumors. Based on the potential cross-talk between ACVR1 and TβRI pathways and known and predicted off-targets of ACVR1 inhibi

SUBMITTER: Cao H 

PROVIDER: S-EPMC7145857 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature