The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development
Author
Xing, Tiaosi; Hass, Daniel T.; Zhang, Samuel S.; Barnstable, Colin J.
Abstract
The transition of rod precursor cells to post-mitotic rod photoreceptors can be promoted by extrinsic factors such as insulin-like growth factor 1 (IGF- 1), which regulates phosphatidylinositide concentration, and consequently the 3- phosphoinositide-dependent protein kinase-1 (PDPK-1). PDPK-1 is a 63 kDa cytoplasmic kinase that controls cell proliferation and differentiation. In the mouse retina, PDPK-1 and its phosphorylated derivative p-PDPK-1 (Ser241), showed peak expression during the first postnatal (PN) day with a substantial decline by PN7 and in the adult retina. Though initially widely distributed among cell types, PDPK-1 expression decreased first in the inner retina and later in the outer retina. When PDPK-1 is inhibited in neonatal retinal explants by BX795, there is a robust increase in rod photoreceptor numbers. The increase in rods depended on the activity of PKC, as BX795 had no effect when PKC is inhibited. Inhibition of PDPK-1-dependent kinases, such as P70-S6K, but not others, such as mTORC-1, stimulated rod development. The P70-S6K-dependent increase in rods appears to be correlated with phosphorylation of Thr252 and not at Thr389, a substrate of mTORC-1. This pathway is also inactive while PKC activity is inhibited. We also found that inhibition of the kinase mTORC-2, also stimulated by insulin activity, similarly increased rod formation, and this effect appears to be independent of PKC activity. This may represent a novel intracellular signaling pathway that also stimulates photoreceptor development. Consistent with previous studies, stimulation of STAT3 activity is sufficient to prevent any PDPK-1, P70-S6K, or mTORC2-dependent increase in rods. Together the data indicate that PDPK-1 and other intrinsic kinases downstream of IGF-1 are key regulators of rod photoreceptor formation.
Date
2018-10-10
Citation:
APA:
Xing, Tiaosi, & Hass, Daniel T., & Zhang, Samuel S., & Barnstable, Colin J.. (October 2018).
The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/7898
MLA:
Xing, Tiaosi, and Hass, Daniel T., and Zhang, Samuel S., and Barnstable, Colin J..
"The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development". .
. (),
October 2018.
April 29, 2024.
http://hdl.handle.net/10342/7898.
Chicago:
Xing, Tiaosi and Hass, Daniel T. and Zhang, Samuel S. and Barnstable, Colin J.,
"The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development," , no.
(October 2018),
http://hdl.handle.net/10342/7898 (accessed
April 29, 2024).
AMA:
Xing, Tiaosi, Hass, Daniel T., Zhang, Samuel S., Barnstable, Colin J..
The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development. .
October 2018;
():
.
http://hdl.handle.net/10342/7898. Accessed
April 29, 2024.
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