Abstract 2339 The Role of an Intermediate Conformation of SHP2 in the MEK Pathway of KRAS-Driven Cancers

Tyrosine phosphatase (SHP2) in conjunction with the MEK (Methyl Ethyl Ketone) pathway causes an increased reproduction rate of cancerous cells in KRAS-driven (Kristen Rat Sarcoma Virus) cancers. SHP2 is a nonreceptor downstream signal transductor protein that promotes cellular development and reproduction when active. The inhibition of the MEK pathway reduces cell growth - and therefore tumor growth as well - initially reduced by the inhibition of growth hormones and SHP2. Normally, SHP2 remains inactive through self-inhibition, but can become activated through other factors. We are currently researching the third transient conformation of SHP2, which seems to be a so called "middle ground" between these active and inactive states. The intermediate conformation could be important to determine the activity of SHP2 and potential cancer treatments. The Moeller Molecular Modeling Team, with support from 3D Molecular Designs and in conjunction with Dr. Jiajie Diao at the University of Cincinnati Medical College, used 3D modeling and printing technology to study the three conformations of SHP2 and its effect on KRAS-driven cancers.