MASTL
Function
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.
Involvement in disease
Defects in MASTL may play a role in the pathogenesis of thrombocytopenia, a disorder defined by reduced number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.
Post-translational modifications
Phosphorylation at Thr-741 by CDK1 during M phase activates its kinase activity (By similarity). Maximum phosphorylation occurs in prometaphase.
Sequence Similarities
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
Cellular localization
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Nucleus
- Cleavage furrow
- During interphase is mainly nuclear, upon nuclear envelope breakdown localizes at the cytoplasm and during mitosis at the centrosomes. Upon mitotic exit moves to the cleavage furrow.
Alternative names
GW, GWL, THC2, MASTL, Serine/threonine-protein kinase greatwall, hGWL, Microtubule-associated serine/threonine-protein kinase-like, MAST-L