| Structural highlights
5yf4 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| NonStd Res: | |
| Gene: | MOB4, MOB3, MOBKL3, PHOCN, PREI3, CGI-95 (HUMAN) |
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[PHOCN_HUMAN] May play a role in membrane trafficking, specifically in membrane budding reactions. [STK26_HUMAN] Mediator of cell growth (PubMed:11641781, PubMed:17360971). Modulates apoptosis (PubMed:11641781, PubMed:17360971). In association with STK24 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006).[1] [2] [3]
Publication Abstract from PubMed
The mammalian STE20-like protein kinase 1 (MST1)-MOB kinase activator 1 (MOB1) complex has been shown to suppress the oncogenic activity of Yes-associated protein (YAP) in the mammalian Hippo pathway, which is involved in the development of multiple tumors including pancreatic cancer (PC). However, it remains unclear whether other MST-MOB complexes are also involved in regulating Hippo-YAP signaling and have potential roles in PC. Here, we report that mammalian STE20-like kinase 4 (MST4), a distantly related ortholog of the MST1 kinase, forms a complex with MOB4 in a phosphorylation-dependent manner. We found that the overall structure of the MST4-MOB4 complex resembles that of the MST1-MOB1 complex, even though the two complexes exhibited opposite biological functions in PC. In contrast to the tumor-suppressor effect of the MST1-MOB1 complex, the MST4-MOB4 complex promoted growth and migration of PANC-1 cells. Moreover, expression levels of MST4 and MOB4 were elevated in PC and were positively correlated with each other, whereas MST1 expression was down-regulated. Owing to divergent evolution of key interface residues, MST4 and MOB4 could disrupt assembly of the MST1-MOB1 complex through alternative pairing and thereby increased YAP activity. Collectively, these findings identify the MST4-MOB4 complex as a noncanonical regulator of the Hippo-YAP pathway with an oncogenic role in PC. Our findings highlight that although MST-MOB complexes display some structural conservation, they functionally diverged during their evolution.
The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer.,Chen M, Zhang H, Shi Z, Li Y, Zhang X, Gao Z, Zhou L, Ma J, Xu Q, Guan J, Cheng Y, Jiao S, Zhou Z J Biol Chem. 2018 Aug 2. pii: RA118.003279. doi: 10.1074/jbc.RA118.003279. PMID:30072378[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin JL, Chen HC, Fang HI, Robinson D, Kung HJ, Shih HM. MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway. Oncogene. 2001 Oct 4;20(45):6559-69. doi: 10.1038/sj.onc.1204818. PMID:11641781 doi:http://dx.doi.org/10.1038/sj.onc.1204818
- ↑ Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, Zhang Y, Han X, Ma D. PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway. Mol Biol Cell. 2007 Jun;18(6):1965-78. Epub 2007 Mar 14. PMID:17360971 doi:10.1091/mbc.E06-07-0608
- ↑ Mardakheh FK, Self A, Marshall CJ. RHO binding to FAM65A regulates Golgi reorientation during cell migration. J Cell Sci. 2016 Dec 15;129(24):4466-4479. doi: 10.1242/jcs.198614. Epub 2016 Nov, 2. PMID:27807006 doi:http://dx.doi.org/10.1242/jcs.198614
- ↑ Chen M, Zhang H, Shi Z, Li Y, Zhang X, Gao Z, Zhou L, Ma J, Xu Q, Guan J, Cheng Y, Jiao S, Zhou Z. The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer. J Biol Chem. 2018 Aug 2. pii: RA118.003279. doi: 10.1074/jbc.RA118.003279. PMID:30072378 doi:http://dx.doi.org/10.1074/jbc.RA118.003279
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