Unique dependence on Sos1 in Kras ^G12D -induced leukemogenesis.

ABSTRACT: We and others have previously shown that Kras ^G12D is a much more potent oncogene than oncogenic Nras in hematological malignancies. We attributed the strong leukemogenic activity of Kras^G12D at least partially to its unique capability to hyperactivate wild-type (WT) Nras and Hras. Here, we report that Sos1, a guanine nucleotide exchange factor, is required to mediate this process. Sos1 is overexpressed in Kras ^G12D/+ cells, but not in Nras ^Q61R/+ and Nras ^G12D/+ cells. Kras^G12D proteins form a complex with Sos1 in vivo. Sos1 deficiency attenuates hyperactivation of WT Nras, Hras, and the downstream ERK signaling in Kras ^G12D/+ cells. Thu

SUBMITTER: You X 

PROVIDER: S-EPMC6293870 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature