Interaction between Mnk2 and CBC(VHL) ubiquitin ligase E3 complex.
MAP kinase-interacting kinase-2 (Mnk2) is one of the downstream kinases activated by MAP kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), although the role of eIF4E phosphorylation and the role of Mnk2 in the process of protein translation are not well understood. Except for eIF4E, other physiological substrates of Mnk2 are still unidentified. To look for these unidentified substrates and to reveal the physiological function of Mnk2, we performed a yeast two-hybrid screening with Mnk2 as the bait. The results demonstrated Mnk2 could interact with VHL (von Hippel-Lindau tumor suppressor), Rbx1 (ring-box 1) and Cul2 (Cullin2) proteins in yeast cells. Furthermore, we validated the interaction between Mnk2 and VHL proteins in mammalian cells by co-immunoprecipitation analysis. Because the three proteins VHL, Rbx1 and Cul2 are all components of the CBC(VHL) ubiquitin ligase E3 complex, it has been shown that Mnk2 can interact with CBC(VHL) complex, and is probably one of the new substrates of the CBC(VHL) complex. Furthermore, during the interaction of Mnk2 with von Hippel-Lindau (VHL) tumor suppressor- binding protein 1 (VBP1), it appears that Mnk2 also joins to modulate cell shape as VBP1 plays an important role in the process of the maturation of the cytoskeleton and in the process of morphogenesis.
Wang
Pingzhang
P
Chinese National Human Genome Center, Beijing 100176, China. sicau2000@yahoo.com.cn
Wang
Xin
X
Wang
Feng
F
Cai
Tianjing
T
Luo
Ying
Y
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape / Q000502:physiology; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
C105153:CUL2 protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; C479529:RBX1 protein, human; D011994:Recombinant Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C486342:MKNK2 protein, human; D017346:Protein Serine-Threonine Kinases; C497446:VHL protein, human