The Ran binding protein RanBPM interacts with TrkA receptor.
RanBPM as a novel binding protein can interact with neurotrophin receptor p75NTR and tyrosine kinase receptor Met which has a similar tyrosine kinase structure as receptor TrkA has. Whether RanBPM interacts with neurotrophin receptor TrkA has not been established to date. In this study, using yeast two-hybrid system, it was identified that RanBPM bound to the intracellular domain (ICD) of neurotrophin receptor TrkA through its SPRY motif. We confirmed the formation of complexes between RanBPM and TrkA by co-immunoprecipitation studies and GST pull-down assays. The region of TrkA interacted with the SPRY domain of RanBPM was located in its tyrosine kinase domain. Furthermore, coimmunoprecipitaiton revealed endogenous RanBPM and receptors TrkA did interact in several mammalian cell lines. It was found that the overexpression of RanBPM could inhibit NGF-induced increase of nuclear factor of activated T cells (NFAT) dependent luciferase expression through its interaction with receptor TrkA, and NFAT transcriptional activity plays an important role in neuronal signal transduction. These data suggested that RanBPM could participate in neurotrophin-mediated gene transcription and expression by its binding to TrkA.
Yuan
Yuhe
Y
National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Fu
Chengbo
C
Chen
Hong
H
Wang
Xin
X
Deng
Weiwei
W
Huang
Bing-Ren
BR
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular / Q000379:methods; D003598:Cytoskeletal Proteins; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D020798:Two-Hybrid System Techniques; D015003:Yeasts; D020931:ran GTP-Binding Protein / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; C116005:Ran binding protein 9; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020931:ran GTP-Binding Protein