Role of p190RhoGAP in Glioma Formation
We have previously shown that expression and activation of the Src family kinase Fyn is necessary for oligodendrocytes to differentiate from progenitor into mature cells. We next searched for Fyn substrates in oligodendrocytes. Use of a yeast 2-hybrid screen yielded p190RhoGAP, a protein known to regulate Rho family members. We showed that p190 is a substrate for Fyn in oligodendrocytes, and then when it is phosphorylated, its GAP activity is increased.
p190RhoGAP maps to position 19q13.3 in the human chromosome, a region that is frequently deleted in human oligodendrogliomas. We therefore postulated that loss of p190 and/or its activity promotes gliomagenesis. In support of this hypothesis, we have recently shown that introduction of the p190 GAP domain into a mouse model for gliomagenesis strongly inhibits glioma formation. Additional experiments are underway to determine the mechanism of p190RhoGAP action, as well as Rho family members, during tumor formation.
