| First Author | Pinzon-Guzman C | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 50 | Pages | 18606-17 |
| PubMed ID | 22171059 | Mgi Jnum | J:178898 |
| Mgi Id | MGI:5300611 | Doi | 10.1523/JNEUROSCI.2578-11.2011 |
| Citation | Pinzon-Guzman C, et al. (2011) Specific protein kinase C isoforms are required for rod photoreceptor differentiation. J Neurosci 31(50):18606-17 |
| abstractText | 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-beta1 and PKC-gamma 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-beta1 and PKC-gamma 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. |
