Photoreceptor neuroprotection: Regulation of akt activation through serine/threonine phosphatases, PHLPP and PHLPPL

Raju V.S. Rajala, Yogita Kanan, Robert E. Anderson

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Serine/threonine kinase Akt is a downstream effector of insulin receptor/ PI3K pathway that is involved in many processes, including providing neuroprotection to stressed rod photoreceptor cells. Akt signaling is known to be regulated by the serine/threonine phosphatases, PHLPP (PH domain and leucine rich repeat protein phosphatase) and PHLPPL (PH domain and leucine rich repeat protein phosphatase-like). We previously reported that both phosphatases are expressed in the retina, as well as in photoreceptor cells. In this study, we examined the PHLPP and PHLPPL phosphatase activities towards non-physiological and physiological substrates. Our results suggest that PHLPP was more active than PHLPPL towards non-physiological substrates, whereas both PHLPP and PHLPP dephosphorylated the physiological substrates of Akt1 and Akt3 with similar efficiencies. Our results also suggest that knockdown of PHLPPL alone does not increase Akt phosphorylation, due to a compensatory increase of PHLPP, which results in the dephosphorylation of Akt. Therefore, PHLPP and PHLPPL regulate Akt activation together when both phosphatases are expressed.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages419-424
Number of pages6
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume854
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Activation
  • Akt
  • Neuroprotection
  • PHLPP
  • PHLPPL
  • Phosphatases
  • Photoreceptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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