Reactome: A Curated Pathway Database
Attention
The EBI data centre will be shutting down from the afternoon (BST) of Friday 26th August until the afternoon of Tuesday 30th August 2016 for essential maintenance. This might have an impact on some Reactome services and we apologize for any inconvenience.

Regulation of PLK1 Activity at G2/M Transition

Stable Identifier
R-HSA-2565942
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The kinase activity of PLK1 is required for cell cycle progression as PLK1 phosphorylates and regulates a number of cellular proteins during mitosis. Centrosomic AURKA (Aurora A kinase), catalytically activated through AJUBA facilitated autophosphorylation on threonine residue T288 at G2/M transition (Hirota et al. 2003), activates PLK1 on centrosomes by phosphorylating threonine residue T210 of PLK1, critical for PLK1 activity (Jang et al. 2002), in the presence of BORA (Macurek et al. 2008, Seki et al. 2008). Once activated, PLK1 phosphorylates BORA and targets it for ubiquitination mediated degradation by SCF-beta-TrCP ubiquitin ligases. Degradation of BORA is thought to allow PLK1 to interact with other substrates (Seki, Coppinger, Du et al. 2008, Seki et al. 2008).

The interaction of PLK1 with OPTN (optineurin) provides a negative-feedback mechanism for regulation of PLK1 activity. Phosphorylated PLK1 binds and phosphorylates OPTN associated with the Golgi membrane GTPase RAB8, promoting dissociation of OPTN from Golgi and translocation of OPTN to the nucleus. Phosphorylated OPTN facilitates the mitotic phosphorylation of the myosin phosphatase subunit PPP1R12A (MYPT1) and myosin phosphatase activation (Kachaner et al. 2012). The myosin phosphatase complex dephosphorylates threonine residue T210 of PLK1 and inactivates PLK1 (Yamashiro et al. 2008).

Literature References
Participants
Participant Of
hasEvent
Orthologous Events