PathwayStep4639 PathwayStep4640 PathwayStep4642 PathwayStep4641 p-S62-ARPP19/p-S67-ENSA binds PP2A-PPP2R2D CDK1 phosphorylates MASTL MASTL (GWL) phosphorylates ARPP19 MASTL phosphorylates ENSA MASTL Facilitates Mitotic Progression Authored: Orlic-Milacic, M, 2012-09-04 Edited: Gillespie, ME, 2012-09-14 Pubmed16600872 Pubmed20538976 Pubmed21164013 Pubmed21164014 Pubmed21444715 Pubmed22354989 Reactome Database ID Release 432465910 Reactome, http://www.reactome.org ReactomeREACT_150182 Reviewed: Burgess, A, 2012-09-28 Reviewed: Mochida, Satoru, 2012-09-26 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).<br><br>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).<br><br>