Serine/threonine-protein kinase greatwall

Definition

Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance. Acts by promoting the inactivation of protein phosphatase 2A (PP2A) during M phase: does not directly inhibit PP2A but acts by mediating phosphorylation and subsequent activation of ARPP19 and ENSA at 'Ser-62' and 'Ser-67', respectively. ARPP19 and ENSA are phosphatase inhibitors that specifically inhibit the PPP2R2D (PR55-delta) subunit of PP2A. Inactivation of PP2A during M phase is essential to keep cyclin-B1-CDK1 activity high. Following DNA damage, it is also involved in checkpoint recovery by being inhibited. Phosphorylates histone protein in vitro; however such activity is unsure in vivo. May be involved in megakaryocyte differentiation.

References:

[1]. Suzanne Vigneron, et al. Greatwall maintains mitosis through regulation of PP2A. EMBO J. 2009 Sep 16;28(18):2786-93. [Content Brief]

[2]. Manish J Gandhi, et al. FLJ14813 missense mutation: a candidate for autosomal dominant thrombocytopenia on human chromosome 10. Hum Hered. 2003;55(1):66-70. [Content Brief]

[3]. Erik Voets, et al. MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis. Cell Cycle. 2010 Sep 1;9(17):3591-601. [Content Brief]

[4]. Priscila V Castilho, et al. The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites. Mol Biol Cell. 2009 Nov;20(22):4777-89. [Content Brief]

[5]. Andrew Burgess, et al. 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 Jul 13;107(28):12564-9. [Content Brief]

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