PKCζ regulates Notch receptor routing and activity in a Notch signaling-dependent manner

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Sjöqvist M, Antfolk D, Ferraris S, Rraklli V, Haga C, Antila C, Mutvei A, Imanishi SY, Holmberg J, Jin S, Eriksson JE, Lendahl U, Sahlgren C
Förläggare: Nature Publishing Group
Publiceringsår: 2014
Tidskrift: Cell Research
Tidskriftsakronym: Cell Res
Volym: 24
Nummer: 4
Artikelns första sida, sidnummer: 433
Artikelns sista sida, sidnummer: 450
ISSN: 1748-7838
eISSN: 1748-7838


Abstrakt

Activation of Notch signaling requires intracellular routing of the receptor, but the mechanisms controlling the distinct steps in the routing process is poorly understood. We identify PKCζ as a key regulator of Notch receptor intracellular routing. When PKCζ was inhibited in the developing chick central nervous system and in cultured myoblasts, Notch-stimulated cells were allowed to undergo differentiation. PKCζ phosphorylates membrane-tethered forms of Notch and regulates two distinct routing steps, depending on the Notch activation state. When Notch is activated, PKCζ promotes re-localization of Notch from late endosomes to the nucleus and enhances production of the Notch intracellular domain, which leads to increased Notch activity. In the non-activated state, PKCζ instead facilitates Notch receptor internalization, accompanied with increased ubiquitylation and interaction with the endosomal sorting protein Hrs. Collectively, these data identify PKCζ as a key regulator of Notch trafficking and demonstrate that distinct steps in intracellular routing are differentially modulated depending on Notch signaling status.

Senast uppdaterad 2020-07-07 vid 06:21