Rajala Raju V S, Kanan Yogita, Anderson Robert E
Department of Ophthalmology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA.
Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd., 73104, Oklahoma City, OK, USA.
Adv Exp Med Biol. 2016;854:419-24. doi: 10.1007/978-3-319-17121-0_55.
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.
丝氨酸/苏氨酸激酶Akt是胰岛素受体/PI3K途径的下游效应器，参与许多过程，包括为应激的视杆光感受器细胞提供神经保护。已知Akt信号传导受丝氨酸/苏氨酸磷酸酶PHLPP（PH结构域和富含亮氨酸重复序列的蛋白磷酸酶）和PHLPPL（PH结构域和富含亮氨酸重复序列的蛋白磷酸酶样）调节。我们先前报道这两种磷酸酶在视网膜以及光感受器细胞中均有表达。在本研究中，我们检测了PHLPP和PHLPPL对非生理性和生理性底物的磷酸酶活性。我们的结果表明，PHLPP对非生理性底物的活性比PHLPPL更高，而PHLPP和PHLPP对Akt1和Akt3的生理性底物去磷酸化的效率相似。我们的结果还表明，单独敲低PHLPPL不会增加Akt磷酸化，因为PHLPP的代偿性增加导致Akt去磷酸化。因此，当两种磷酸酶均表达时，PHLPP和PHLPPL共同调节Akt激活。
