Discovery published in Cell was made by generating and applying active and kinase-deficient kinome collection.
A group of scientists have identified two novel kinases regulating the Hedgehog signaling (Hh) pathway, which has been linked to multiple types of human cancer. They also identified a novel kinase required for activation of Kaposis sarcoma herpesvirus.
The team cloned a number of predicted human protein kinase genes in functional form and then used kinases lacking catalytic activity generated from this cloning. “To allow genome-scale identification of genes that regulate cellular signaling, we cloned >90% of all human full-length protein kinase cDNAs and constructed the corresponding kinase activity-deficient mutants,” the researchers write.
The investigators then used the kinome collection in several high-throughput screens including a screen that found that MAP3K10 and DYRK2 regulate Hh pathway. “DYRK2 directly phosphorylated and induced the proteasome-dependent degradation of the key Hh pathway-regulated transcription factor, GLI2. MAP3K10, in turn, affected GLI2 indirectly by modulating the activity of DYRK2 and the known Hh pathway component GSK3b,” they add.
The investigators involved in the study were from National Public Health Institute, University of Helsinki, VTT Technical Research Centre of Finland, University of Turku, OriGene Technologies, Radboud University Nijmegen. The study is published in the May 2 issue of Cell.