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Journal of Lipid Research, Vol. 51, 4-22, January 2010
Copyright © 2010 by American Society for Biochemistry and Molecular Biology

Thematic Review

Phosphoinositide 3-kinase signaling in the vertebrate retina

Raju V. S. Rajala¹

Departments of Ophthalmology and Cell Biology, and Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104

¹ To whom correspondence should be addressed. e-mail: raju-rajala{at}ouhsc.edu

The phosphoinositide (PI) cycle, discovered over 50 years ago by Mabel and Lowell Hokin, describes a series of biochemical reactions that occur on the inner leaflet of the plasma membrane of cells in response to receptor activation by extracellular stimuli. Studies from our laboratory have shown that the retina and rod outer segments (ROSs) have active PI metabolism. Biochemical studies revealed that the ROSs contain the enzymes necessary for phosphorylation of phosphoinositides. We showed that light stimulates various components of the PI cycle in the vertebrate ROS, including diacylglycerol kinase, PI synthetase, phosphatidylinositol phosphate kinase, phospholipase C, and phosphoinositide 3-kinase (PI3K). This article describes recent studies on the PI3K-generated PI lipid second messengers in the control and regulation of PI-binding proteins in the vertebrate retina.

Abbreviations: AMD, age-related macular degeneration; BDNF, brain derived neurotrophic factor; bFGF, basic fibroblast growth factor; CNTF, ciliary neurotrophic factor; DG, diacylglycerol; DHA, docosahexaenoic acid; 4E-BP, eukaryotic translation initiation factor 4E binding protein; eIF, eukaryotic initiation factor; EPO, erythropoietin; GPCR, G-protein coupled receptor; Grb14, growth factor receptor-bound protein 14; GSK3, glycogen synthase kinase 3; IGF-1, insulin like growth factor 1; IP₃, inositol 1,4,5-trisphosphate; IR, insulin receptor; IRS, insulin receptor substrate; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; PDGF, platelet-derived growth factor; PDK1, phosphoinositide-dependent protein kinase-1; PH, pleckstrin homology; PHR1, p leckstrin h omology domain r etinal protein; PI, phosphatidylinositol; PI-3,4 P2, phosphatidylinositol 3,4-bisphosphate; PI-3,4,5-P3, phosphatidylinositol 3,4,5-trisphosphate; PI3K, phosphoinositide 3-kinase; PI-3-P, phosphatidylinositol 3-phosphate; PI-4,5-P2, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C; PLC, phospholipase C; p70S6K, ribosomal protein S6 kinase; PTEN, phosphatase and tensin homolog; PTP, protein tyrosine phosphatase; RGC, retinal ganglion cell; ROS, rod outer segment; RPE, retinal pigmented epithelium; SH, Src homology; VSP34, vacuole sorting protein 34; 4E-BP, eukaryotic initiation factor 4E binding protein

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