Disease relevance of wts

• The absence of wts function also results in apical hypertrophy of imaginal disc epithelial cells [1].

High impact information on wts

• The tumor suppressors Merlin, expanded, hippo, salvador and mob as tumor suppressor also share multiple Fat pathway phenotypes but regulate Warts activity independently [2].
• Thus, Yki is a critical target of the Wts/Lats protein kinase and a potential oncogene [3].
• In Drosophila, these two processes are regulated by a pathway involving the Ste20-like kinase Hippo (Hpo) and the NDR family kinase Warts (Wts; also called Lats) [3].
• Recent studies have identified the Large tumor suppressor (Lats)/Warts (Wts) protein kinase as a key component of a pathway that controls the coordination between cell proliferation and apoptosis [4].
• The growth regulators warts/lats and melted interact in a bistable loop to specify opposite fates in Drosophila R8 photoreceptors [5].

Biological context of wts

• However, the mechanisms by which sav and wts regulate growth and apoptosis are not well understood [6].
• Because of the excess growth and abnormalities of differentiation that follow homozygous loss, we consider wts to be a tumor suppressor gene [1].
• One wts allele allows survival of homozygotes to the late larval stage, and these larvae show extensive imaginal disc overgrowth [1].
• The wts gene is defined by the breakpoints of overlapping deficiencies in the right telomeric region of chromosome 3, region 100A, and by lethal P-element insertions and excisions [1].
• Animals having mutations in both dcsk and lats display cell overproliferation phenotypes more severe than either mutant alone, demonstrating these genes function together in vivo to regulate cell numbers [7].

Anatomical context of wts

• Therefore, we suggest a potential in vivo mechanism of LATS1 activation through rapid recruitment to the plasma membrane by hMOB1 followed by multi-site phosphorylation, thereby providing insight into the molecular regulation of the LATS tumour suppressor [8].

Associations of wts with chemical compounds

• Two genes that function together to regulate growth, proliferation, and apoptosis in Drosophila are warts (wts), encoding a serine/threonine kinase, and salvador (sav), encoding a WW domain containing Wts-interacting protein [6].
• Based on staining with PY and DIg antibodies, the apico-lateral junctional complexes appeared normal in tissue from the hyperplastic overgrowth mutants fat, dco, gd and wts [9].
• The LATS family of serine/threonine kinases control tissue size by regulating cell proliferation and function as tumor suppressor genes in both Drosophila and mammals [7].
• Finally, we show that dCSK phosphorylates LATS in vitro at a conserved C-terminal tyrosine residue, which is critical for normal LATS function in vivo [7].

Regulatory relationships of wts

• Fat modulates Salvador/Warts/Hippo pathway activity by promoting abundance and localization of Expanded protein at the apical membrane of epithelial tissues [10].

Other interactions of wts

• Both Mer and Ex are members of the Band 4.1 protein superfamily, and, based on analyses of mer ex double mutants, they are proposed to function together in at least a partially redundant manner upstream of the Hippo (Hpo) and Warts (Wts) proteins to regulate cell growth and division [11].
• A genetic screen for modifiers of the lats tumor suppressor gene identifies C-terminal Src kinase as a regulator of cell proliferation in Drosophila [7].

Analytical, diagnostic and therapeutic context of wts

• A newly emerging signaling pathway that controls organ size during development is the Salvador/Warts/Hippo pathway [10].
• Homozygous dcsk mutants have enlarged tissue phenotypes similar to lats and FACS and immunohistochemistry analysis of these tissues revealed that dcsk also regulates cell proliferation during development [7].

References