| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 8298453 | Biochemistry and Biophysics Reports | 2018 | 10 Pages |
Abstract
Preliminary screening data showed that the ShcD adaptor protein associates with the proto-oncogene RET receptor tyrosine kinase. In the present study, we aimed to investigate the molecular interaction between ShcD and RET in human neuroblastoma cells and study the functional impact of this interaction. We were able to show that ShcD immunoprecipitated with RET from SK-N-AS neuroblastoma cell lysates upon GDNF treatment. This result was validated by ShcD-RET co-localization, which was visualized using a fluorescence microscope. ShcD-RET coexpression promoted ShcD and RET endosomal localization, resulting in unexpected inhibition of the downstream ERK and AKT pathways. Interestingly, ShcD-RET association reduced the viability and migration of SK-N-AS cells. Although ShcD was previously shown to trigger melanoma cell migration and tumorigenesis, our data showed an opposite role for ShcD in neuroblastoma SK-N-AS cells via its association with RET in GDNF-treated cells. In conclusion, ShcD acts as a switch molecule that promotes contrasting biological responses depending on the stimulus ad cell type.
Keywords
GDNF Family LigandsFBS,eGFR,DNA,PVDF,MAPK, EGF,GDNFPMSF,GFP, RT, ECL,PDGF, SDS-PAGE, ERK,DMEM,mAb, Phospho-tyrosineProto-oncogene tyrosine-protein kinase SrcG-protein coupled receptorHRP,PBS, Monoclonal antibodyPolyclonal antibodydeoxyribonucleic acidsodium dodecylsulphate polyacrylamide gel electrophoresisEndosomesrevolution per minuteenhanced chemiluminescenceRETRearranged during transfectionminuteRoom temperaturehoursfetal bovine serumcytomegalovirusnon-fat dry milkepidermal growth factorInsulin growth factorplatelet-derived growth factorphosphoinositide 3-kinasephenylmethylsulfonyl fluorideAnaplastic lymphoma kinaseLuria-BertaniPhosphate-buffered salineMAP, NeuroblastomaHorseradish peroxidasemitogen-activated proteingreen fluorescent proteinprotein kinase Bgrowth factor receptor-bound protein 2Polyvinylidene fluorideMuscle specific kinasemitogen-activated protein kinasesExtracellular signal–regulated kinasesTyrosine kinase receptorReceptor Tyrosine Kinasehepatocyte growth factor receptorEpidermal growth factor receptorFibroblast growth factor receptors
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Authors
Zeanap A. Mabruk, Samrein B.M. Ahmed, Asha Caroline Thomas, Sally A. Prigent,