5YF4

A kinase complex MST4-MOB4

Summary for 5YF4

• Entry DOI: 10.2210/pdb5yf4/pdb
• Descriptor: MOB-like protein phocein, Peptide from Serine/threonine-protein kinase 26, ZINC ION, ... (4 entities in total)
• Functional Keywords: kinase, complex, phosphorylation, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 21159.67

Authors

Chen, M.,Zhou, Z.C. (deposition date: 2017-09-20, release date: 2018-08-15, Last modification date: 2024-10-30)

Primary citation

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.C.
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., 293:14455-14469, 2018

PubMed Abstract: 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. Because of 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.

PubMed: 30072378
DOI: 10.1074/jbc.RA118.003279

Experimental method

X-RAY DIFFRACTION (1.897 Å)