serine/threonine protein kinase greatwall; GW; GWL; hGWL; microtubule-associated serine/threonine protein kinase-like; MAST-L (MASTL, GW, GWL, THC2)
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Function
- serine/threonine kinase
- role in M phase by acting as a regulator of mitosis entry & maintenance
- acts by promoting inactivation of protein phosphatase 2A (PP2A) during M phase:
- does not directly inhibit PP2A but acts by mediating phosphorylation & subsequent activation of ARPP19 at Ser-62 & ENSA at Ser-67
- ARPP19 & 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, MASTL is also involved in checkpoint recovery
- phosphorylates histone protein in vitro
- may be involved in megakaryocyte differentiation
- phosphorylation at Thr-741 by CDK1 during M phase activates its kinase activity (putative)
- maximum phosphorylation occurs in prometaphase
Structure
- belongs to the protein kinase superfamily, AGC Ser/Thr protein kinase family
- contains 1 AGC-kinase C-terminal domain
- contains 1 protein kinase domain
Compartment
- cytoplasm, cytoskeleton, centrosome, nucleus
- cleavage furrow
- during interphase is mainly nuclear
- upon nuclear envelope breakdown localizes in the cytoplasm & during mitosis at the centrosomes
- upon mitotic exit, moves to the cleavage furrow
Alternative splicing
named isoforms=3
Pathology
- defects in MASTL are the cause of thrombocytopenia type 2
Notes
- reduced levels of MASTL by RNAi
- causes a delay in G2 phase & slow chromosome condensation
- cells that enter & progress through mitosis often fail to completely separate their sister chromatids in anaphase leading to the formation of 4N G1 cells subsequent to failure of cytokinesis