title: Specific protein kinase C isoforms are required for rod photoreceptor differentiation.
abstract: The protein kinase C (PKC) family of enzymes regulates cell physiology through phosphorylation of serine and threonine residues of many proteins in most cell types. Here we identify PKC-β1 and PKC-γ as isoforms that are essential for rod photoreceptor differentiation in mouse retinas. Using ex vivo retinal explants, we found that phorbol ester 12-myristate 13-acetate and insulin-like growth factor 1 (IGF1) induced rod differentiation, as defined by opsin or Crx expression, in a PKC-dependent manner days ahead of rod development in untreated explants. PKC-β1 and PKC-γ were colocalized with proliferating cell nuclear antigen (PCNA)- and STAT3-positive progenitors through the later differentiation period. Pharmacological or genetic inhibition of either isoform resulted in a partial reduction in the appearance of rods, whereas removing both isoforms resulted in their complete absence. Furthermore, a significant decline of STAT3 tyrosine phosphorylation was observed by activation of PKC, while inhibition of PKC resulted in an increase of phosphorylated STAT3 along with a delayed cell cycle exit of progenitors with prolonged PCNA expression. In adult retinas, IGF1 activates PI-3 kinase (PI3K), but in neonatal retinas its action is identical to the action of an PI3K inhibitor. These data unveil a novel signaling cascade that coordinates and regulates rod differentiation through specific PKC isoforms in mammals.
authors.affiliation: Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033-2255, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Pinzon-Guzman
authors.forename: Samuel Shao-Min
authors.initials: SS
authors.lastname: Zhang
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Barnstable
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D007334:Insulin-Like Growth Factor I; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate