title: Photoreceptor Neuroprotection: Regulation of Akt Activation Through Serine/Threonine Phosphatases, PHLPP and PHLPPL.
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.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. raju-rajala@ouhsc.edu.|Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd., 73104, Oklahoma City, OK, USA. raju-rajala@ouhsc.edu.|Department of Physiology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. raju-rajala@ouhsc.edu.|Department of Cell Biology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. raju-rajala@ouhsc.edu.
authors.forename: Raju V S
authors.initials: RV
authors.lastname: Rajala
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. ykanan1@jhmi.edu.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Kanan
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. Robert-Anderson@ouhsc.edu.|Department of Cell Biology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA. Robert-Anderson@ouhsc.edu.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Anderson
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D000066829:Neuroprotection; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D009687:Nuclear Proteins; C494918:AKT1 protein, human; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt; C400601:PHLPP1 protein, human; C541572:PHLPP2 protein, human; D010749:Phosphoprotein Phosphatases
keywords: Activation; Akt; Neuroprotection; PHLPP; PHLPPL; Phosphatases; Photoreceptors