Single-molecule study of lateral mobility of epidermal growth factor receptor 2/HER2 on activation.
The transmembrane protein HER2, a member of the epidermal growth factor receptor family of tyrosine kinase, plays important roles in many fundamental cellular processes as well as the pathogenesis of many cancers. In this work, we have applied the single-molecule fluorescence microscopic method to study lateral mobility change of HER2 on activation by imaging and tracking individual GFP-tagged HER2 molecules on the membrane of living cells. The single HER2 molecules displayed different diffusion rates and modes. It was interesting to find that the mobility of HER2 increased upon stimulation by heregulin beta1, the specific ligand of HER3. The faster diffusion was related to the tyrosine phosphorylation of HER2 or EGFR. The results provided new information for the understanding of HER2 activation and molecular mechanism of signal transduction through HER2/HER3 heterodimerization.
Xiao
Zeyu
Z
Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China, 100080.
Ma
Xinyong
X
Jiang
Yaxin
Y
Zhao
Zilong
Z
Lai
Bo
B
Liao
Jieying
J
Yue
Jiachang
J
Fang
Xiaohong
X
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020890:Neuregulin-1 / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013050:Spectrometry, Fluorescence / Q000379:methods; D013997:Time Factors; D014407:Tumor Cells, Cultured
D049452:Green Fluorescent Proteins; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; C087230:heregulin beta1; C524056:Erbb2 protein, mouse