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

Yanqiong Zhang; H Shelton Earp; Pengda Liu

doi:10.1080/23723556.2019.1611161

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

Mol Cell Oncol. 2019 May 7;6(4):1611161. doi: 10.1080/23723556.2019.1611161. eCollection 2019.

Authors

Yanqiong Zhang^{1

2}, H Shelton Earp^{1

3}, Pengda Liu^{1

2}

Affiliations

¹ UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Department of Biochemistry and Biophysics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Department of Medicine and Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

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: Akt; Kidney cancer; MERTK; SAV1; drug resistance.

Abstract

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