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The Large Tumor Suppressor (LATS) and 14‐3‐3 Regulate Mixed Lineage Kinase 3 (MLK3) Subcellular Localization
Author(s) -
Kasturirangan Srimathi,
Chadee Deborah N
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb263
Subject(s) - microbiology and biotechnology , subcellular localization , kinase , biology , map kinase kinase kinase , protein kinase a , cancer research , mapk/erk pathway , cell growth , protein kinase r , immunoprecipitation , cytoplasm , mitogen activated protein kinase kinase , cell culture , biochemistry , genetics
Mixed Lineage Kinase 3 (MLK3) is a mitogen‐activated protein (MAP) kinase kinase kinase (MAP3K) that activates multiple MAPK signaling pathways in response to cytokines and stress stimuli. MLK3 is important for ovarian cancer cell proliferation and invasion. However, few upstream regulators of MLK3 are known, and MLK3 subcellular localization in ovarian cells is not well understood. LATS (Large Tumor Suppressor), a Ser/Thr kinase, is activated by cell‐cell contact to inhibit proliferation, and also regulates apoptosis and mitotic exit. We observed that confluent ovarian epithelial cells had high levels of phosphorylated, activated LATS (p‐LATS). Furthermore, ovarian cancer cells had substantially lower amounts of p‐LATS in comparison to ovarian epithelial cells. Using confocal microscopy and cell fractionation, we found that MLK3 is both cytoplasmic and nuclear in ovarian cells. Co‐immunoprecipitation assays indicated that LATS interacts with MLK3 and promotes MLK3/14‐3‐3 association and MLK3 cytoplasmic localization; thereby linking the MAPK and Hippo signaling pathways. In conclusion, our results identify LATS as a novel regulator of MLK3 that affects MLK3 subcellular localization in ovarian epithelial cells. Support or Funding Information R15‐CA199164 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .