Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Biophysical Phenomena
-
Cell Line
-
Cell Membrane / chemistry
-
Cell Membrane / drug effects
-
Cell Membrane / metabolism
-
Dimerization
-
ErbB Receptors / chemistry
-
ErbB Receptors / genetics
-
ErbB Receptors / metabolism
-
Green Fluorescent Proteins / chemistry
-
Green Fluorescent Proteins / genetics
-
Green Fluorescent Proteins / metabolism
-
HeLa Cells
-
Humans
-
Ligands
-
Microscopy, Fluorescence
-
Protein Serine-Threonine Kinases / chemistry*
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism
-
Protein Structure, Quaternary
-
Receptor, Transforming Growth Factor-beta Type II
-
Receptors, Transforming Growth Factor beta / chemistry*
-
Receptors, Transforming Growth Factor beta / genetics
-
Receptors, Transforming Growth Factor beta / metabolism
-
Recombinant Fusion Proteins / chemistry
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Signal Transduction
-
Transforming Growth Factor beta1 / pharmacology
Substances
-
Ligands
-
Receptors, Transforming Growth Factor beta
-
Recombinant Fusion Proteins
-
Transforming Growth Factor beta1
-
Green Fluorescent Proteins
-
ErbB Receptors
-
Protein Serine-Threonine Kinases
-
Receptor, Transforming Growth Factor-beta Type II