Mo25 is the Drosophila ortholog of the MO25/CAB39 armadillo-repeat scaffold protein. Together with the pseudokinase Stlk (STRAD), it forms a heterotrimeric complex with the tumor-suppressor kinase LKB1 that stabilizes LKB1 in an active conformation, so that the complex phosphorylates and activates AMPK and AMPK-related kinases and thereby restrains TORC1-dependent growth. Mo25 is cytoplasmic and can be recruited to the cell cortex by LKB1. In neuroblasts, Mo25 also acts with the GC (germinal center) kinase Fray to control basal localization of the cell-fate determinant Miranda during asymmetric cell division.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | REMOVE | Summary: Root-term ND annotation recording that no molecular function was known at the time. Reason: A stale placeholder. Mo25 already carries the specific molecular function protein serine/threonine kinase activator activity (GO:0043539) by IBA and ISS, and fly co-immunoprecipitation supports its role as an LKB1 cofactor, so the unknown-function root annotation no longer applies. Supporting Evidence: PMID:36899949 We finally tested whether impaired LKB1 T353 phosphorylation results in changes in binding of the LKB1 cofactors Stlk and Mo25, which might explain differences in the activation of LKB1. |
| GO:0005634 nucleus | IDA PMID:18054329 The GC kinase Fray and Mo25 regulate Drosophila asymmetric d... | KEEP AS NON CORE | Summary: Nuclear Mo25 signal reported in the same localization study. Reason: The curators recorded nuclear localization from the full text, which is not visible in the cached abstract; MO25-family proteins can shuttle, but the functional site of the LKB1 complex and of Mo25-Fray signalling is cytoplasmic/cortical. |
| GO:0005737 cytoplasm | IDA PMID:18054329 The GC kinase Fray and Mo25 regulate Drosophila asymmetric d... | ACCEPT | Summary: Mo25 localizes to the cytoplasm of neuroblasts and is relocalized to the cortex by LKB1 overexpression. Reason: Direct localization data; the LKB1-STRAD-MO25 complex acts in the cytoplasm. Supporting Evidence: PMID:18054329 Overexpression of Lkb1, which accumulates in the cell cortex, drastically relocalizes both Mo25 and Fray from the cytoplasm to the cortex |
| GO:0043539 protein serine/threonine kinase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Mo25 acts as a scaffold/activator of LKB1 (and of STE20-family GC kinases such as Fray). Reason: Conserved MO25 function, supported by the PAINT IBA and by fly data showing Mo25 is an LKB1 cofactor that associates with LKB1 and Stlk. In mammals MO25 binding enhances LKB1 activity and nuclear export. Supporting Evidence: PMID:36899949 Although LKB1 has been supposed to be a constitutively active kinase, its export from the nucleus and its activity are enhanced upon binding to the pseudokinase STRADΞ± and to the adaptor protein Mo25 [15,16,17]. PMID:18054329 Drosophila Mo25 interacts with the tumor suppressor kinase Lkb1 in vivo, as have shown in mammals. file:DROME/Mo25/Mo25-deep-research-falcon.md Fly Mo25 enhances the kinase activity of Fray *in vitro* |
| GO:0043539 protein serine/threonine kinase activator activity | ISS PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | ACCEPT | Summary: Mo25 acts as a scaffold/activator of LKB1 (and of STE20-family GC kinases such as Fray). Reason: Conserved MO25 function, supported by the PAINT IBA and by fly data showing Mo25 is an LKB1 cofactor that associates with LKB1 and Stlk. In mammals MO25 binding enhances LKB1 activity and nuclear export. Supporting Evidence: PMID:36899949 Although LKB1 has been supposed to be a constitutively active kinase, its export from the nucleus and its activity are enhanced upon binding to the pseudokinase STRADΞ± and to the adaptor protein Mo25 [15,16,17]. PMID:18054329 Drosophila Mo25 interacts with the tumor suppressor kinase Lkb1 in vivo, as have shown in mammals. file:DROME/Mo25/Mo25-deep-research-falcon.md Fly Mo25 enhances the kinase activity of Fray *in vitro* |
| GO:1902554 serine/threonine protein kinase complex | NAS PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | ACCEPT | Summary: Mo25 is a subunit of the LKB1-Stlk-Mo25 serine/threonine kinase complex. Reason: Co-immunoprecipitation of Stlk and Mo25 with LKB1 in Drosophila S2R+ cells supports membership of this kinase complex; no more specific GO complex term exists for the LKB1-STRAD-MO25 heterotrimer. Supporting Evidence: PMID:36899949 However, no differences in Stlk/Mo25 binding were detectable in co-immunoprecipitation assays (Figure 4G) |
| GO:1904263 positive regulation of TORC1 signaling | TAS PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | MODIFY | Summary: Annotation from a study of LKB1 regulation by PDK1, where the LKB1 complex activates AMPK and thereby lowers mTOR activity. Reason: The LKB1-Stlk-Mo25 complex activates AMPK, which inhibits TORC1; cells with hyperactive (phospho-deficient) LKB1 show decreased mTOR activity. The direction of the annotation is therefore inverted; negative regulation of TORC1 signaling is the appropriate term (matching the Lkb1 review). Proposed replacements: negative regulation of TORC1 signaling Supporting Evidence: PMID:36899949 Cells expressing phospho-deficient LKB1 consequently display enhanced AMPK activation and decreased mTOR activity, resulting in reduced cell size. |
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Download this section (compressed HTML)Mo25 (Mo25) encodes a protein involved in neuroblast asymmetric cell divisions via localization of the product of mira. It physically interacts with the kinase encoded by Lkb1.
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