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MASTL Facilitates Mitotic Progression (R-HSA-2465910) [Homo sapiens]

Pathway
Summation

The activity of MASTL, also known as the Greatwall kinase (GWL), is necessary for the entry and progression of mitosis. MASTL is activated by phosphorylation of several key residues during mitotic entry. Phosphorylation on the serine residue S875 (S883 in Xenopus), likely through autophosphorylation (Blake-Hodek et al. 2012) appears to be critical (Vigneron et al. 2011). Several other sites, including putative CDK1 targets T194, T207 and T741, contribute to the full activation of MASTL (Yu et al. 2006, Blake-Hodek et al. 2012). Other kinases, such as PLK1 (Vigneron et al. 2011) and other MASTL phosphorylation sites may also be functionally important (Yu et al. 2006, Blake-Hodek et al. 2012).

Activated MASTL phosphorylates ARPP19 and ENSA on serines S62 and S67, respectively, enabling them to bind to and inhibit the phosphatase activity of PP2A complexed with the regulatory subunit PPP2R2D (B55-delta). Inhibition of PP2A-PPP2R2D activity by ARPP19 or ENSA prevents dephosphorylation of CDK1 targets, hence allowing entry and maintenance of mitosis (Mochida et al. 2010, Gharbi-Ayachi et al. 2010, Burgess et al. 2010).

Locations in the PathwayBrowser
Additional Information
Compartment nucleoplasm
Literature References
pubMedId Title Journal Year
16600872 Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus egg extracts Mol. Cell 2006
21164013 Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis Science 2010
21164014 The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A Science 2010
20538976 Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance Proc. Natl. Acad. Sci. U.S.A. 2010
21444715 Characterization of the mechanisms controlling Greatwall activity Mol. Cell. Biol. 2011
22354989 Determinants for activation of the atypical AGC kinase Greatwall during M phase entry Mol. Cell. Biol. 2012
Inferred Entries
Orthologous events
 
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