Single-molecule imaging reveals transforming growth factor-beta-induced type II receptor dimerization.
Transforming growth factor-beta (TGF-beta) elicits its signals through two transmembrane serine/threonine kinase receptors, type II (TbetaRII) and type I receptors. It is generally believed that the initial receptor dimerization is an essential event for receptor activation. However, previous studies suggested that TGF-beta signals by binding to the preexisting TbetaRII homodimer. Here, using single molecule microscopy to image green fluorescent protein (GFP)-labeled TbetaRII on the living cell surface, we demonstrated that the receptor could exist as monomers at the low expression level in resting cells and dimerize upon TGF-beta stimulation. This work reveals a model in which the activation of serine-threonine kinase receptors is also accomplished via dimerization of monomers, suggesting that receptor dimerization is a general mechanism for ligand-induced receptor activation.
Zhang
Wei
W
Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
Jiang
Yaxin
Y
Wang
Qiang
Q
Ma
Xinyong
X
Xiao
Zeyu
Z
Zuo
Wei
W
Fang
Xiaohong
X
Chen
Ye-Guang
YG
D055592:Biophysical Phenomena; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D019281:Dimerization; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D053773:Transforming Growth Factor beta1; D049452:Green Fluorescent Proteins; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II