| First Author | Mali RS | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 13 | Pages | 2669-78 |
| PubMed ID | 22806893 | Mgi Jnum | J:189153 |
| Mgi Id | MGI:5444551 | Doi | 10.1182/blood-2011-08-375873 |
| Citation | Mali RS, et al. (2012) Role of SHP2 phosphatase in KIT-induced transformation: identification of SHP2 as a druggable target in diseases involving oncogenic KIT. Blood 120(13):2669-78 |
| abstractText | Intracellular mechanism(s) that contribute to promiscuous signaling via oncogenic KIT in systemic mastocytosis and acute myelogenous leukemia are poorly understood. We show that SHP2 phosphatase is essential for oncogenic KIT-induced growth and survival in vitro and myeloproliferative disease (MPD) in vivo. Genetic disruption of SHP2 or treatment of oncogene-bearing cells with a novel SHP2 inhibitor alone or in combination with the PI3K inhibitor corrects MPD by disrupting a protein complex involving p85alpha, SHP2, and Gab2. Importantly, a single tyrosine at position 719 in oncogenic KIT is sufficient to develop MPD by recruiting p85alpha, SHP2, and Gab2 complex to oncogenic KIT. Our results demonstrate that SHP2 phosphatase is a druggable target that cooperates with lipid kinases in inducing MPD. |
