LATS1/WARTS

Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function. Plays a role in mammary gland epithelial cell differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668).

Autophosphorylated and phosphorylated during M-phase of the cell cycle (PubMed:10518011, PubMed:15122335, PubMed:9988268). Phosphorylated by STK3/MST2 at Ser-909 and Thr-1079, which results in its activation (PubMed:15688006). Phosphorylated by MAP4Ks; in parallel to STK3/MST2 and resulting to its activation (PubMed:26437443). Phosphorylation at Ser-464 by NUAK1 and NUAK2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy (PubMed:19927127).

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.

Expressed in all adult tissues examined except for lung and kidney.

• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Cytoplasm
• Cytoskeleton
• Spindle
• Midbody
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Spindle pole body
• Localizes to the centrosomes throughout interphase but migrates to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, during mitosis.

WARTS, LATS1, Serine/threonine-protein kinase LATS1, Large tumor suppressor homolog 1, WARTS protein kinase, h-warts

• entrezGene:9113
• omim:603473
• swissprot:O95835

Proteins

Oncology

126870Da