title: Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor.
abstract: LATS2 kinase functions as part of the Hippo pathway to promote contact inhibition of growth and tumor suppression by phosphorylating and inhibiting the transcriptional coactivator YAP. LATS2 is activated by the MST2 kinase. How LATS2 is activated by MST2 in response to changes in cell density is unknown. Here we identify the angiomotin-family tight junction protein AMOTL2 as a novel activator of LATS2. Like AMOTL2, the other angiomotin-family proteins AMOT and AMOTL1 also activate LATS2 through a novel conserved domain that binds and activates LATS2. AMOTL2 binds MST2, LATS2, and YAP, suggesting that AMOTL2 might serve as a scaffold protein. We show that LATS2, AMOTL2, and YAP all localize to tight junctions, raising the possibility that clustering of Hippo pathway components at tight junctions might function to trigger LATS2 activation and growth inhibition in response to increased cell density.
authors.affiliation: Department of Microbial and Physiological Systems and Program in Cell Dynamics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Murugan
authors.initials: M
authors.lastname: Paramasivam
authors.forename: Ali
authors.initials: A
authors.lastname: Sarkeshik
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Maria J G
authors.initials: MJ
authors.lastname: Fernandes
authors.forename: Dannel
authors.initials: D
authors.lastname: McCollum
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000091082:Angiomotins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D003260:Contact Inhibition / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000091082:Angiomotins; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000090742:Serine-Threonine Kinase 3; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C423985:AMOT protein, human; C508566:AMOTL2 protein, human; C088374:YAP1 protein, human; C406449:LATS2 protein, human; C097835:STK3 protein, human; D000099317:Hippo Kinases