Ligand-induced polyubiquitination of receptor tyrosine kinases.
The platelet-derived growth factor beta-receptor undergoes polyubiquitination as a consequence of ligand binding. In the present study, we have examined the ligand-induced receptor ubiquitination also in the other receptor tyrosine kinase (structurally different) subfamilies by immunoblotting with anti-ubiquitin antiserum. In addition to the platelet-derived growth factor alpha- and beta-receptors, all the monomeric receptor tyrosine kinases examined, such as the receptors for epidermal growth factor (subfamily I), colony stimulating factor-1 (subfamily III), and fibroblast growth factor (subfamily IV), were found to be ubiquitinated after ligand stimulation. However, the insulin receptor (subfamily II), which is a tetrameric molecule, was not. These data suggest that the ligand-induced polyubiquitination of the receptor is a general phenomenon observed in most of the monomeric receptor tyrosine kinases.
Mori
S
S
Department of Laboratory Medicine, Yamagata University School of Medicine, Japan.
Claesson-Welsh
L
L
Okuyama
Y
Y
Saito
Y
Y
D016475:3T3 Cells; D000818:Animals; D001011:Aorta; D000077214:Becaplermin; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000378:metabolism*; D066246:ErbB Receptors / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000302:isolation & purification / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000302:isolation & purification / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D013552:Swine; D014162:Transfection; D014452:Ubiquitins / Q000378:metabolism*
D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D014452:Ubiquitins; D000077214:Becaplermin; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D016186:Receptor, Macrophage Colony-Stimulating Factor; D017479:Receptors, Platelet-Derived Growth Factor