Beyond growth signaling: apoptotic sensor MERTK activates AKT by a novel mechanism

Abstract

Canonically the oncogenic kinase AKT is activated by growth signals. Our work suggests apoptotic materials, abundant in tumors, also contribute to AKT activation by stimulating MERTK that in turn phosphorylates Y26 in the AKT PH domain. pY26 reverses binding of an AKT endogenous, WW-domain containing inhibitor, SAV1, allowing AKT responsiveness to classic growth signals. This novel mechanism may contribute to drug resistance.

Keywords

• kidney cancer
• drug resistance
• mertk
• akt
• sav1