An altered IGF-I receptor is present in human leukemic cells.
We have characterized and analyzed IGF-I- and insulin-stimulated cell growth, receptor binding, and autophosphorylation in the human leukemic cell line HL-60. IGF-I-stimulated cell growth occurred at low (5 ng/ml) and insulin stimulated only at high (500 ng/ml) concentrations. Binding of 125I-IGF-I to partially purified plasma membrane proteins followed the characteristics of IGF-I receptor binding. 125I-IGF-I binding, as determined by chemical cross-linking, occurred to a 145-kDa protein. IGF-I, as well as insulin, stimulated the autophosphorylation of a 105-kDa band (pp105), but we could not detect a 95-kDa band corresponding to the known molecular mass of the IGF-I and insulin receptor beta-subunits. Phosphorylation of pp105 followed the dose-response characteristics of the IGF-I receptor. The phosphorylation of pp105 occurred at tyrosine and threonine, and the pattern of HPLC tryptic peptide maps showed marked differences when compared with that of a phosphorylated insulin receptor beta-subunit. Enzymatic deglycosylation of pp105 resulted only in a slight reduction of the molecular weight. These data suggest that pp105 is the beta-subunit of an IGF-I receptor variant with a higher molecular weight, similar to that found in fetal tissue. The HL-60 cell may acquire, at least in part, malignant growth characteristics through reexpression of the fetal version of the IGF-I receptor.
Medizinische Klinik III, Universität München, Federal Republic of Germany.
M
M
Kellerer
B
B
Obermaier-Kusser
B
B
Ermel
U
U
Wallner
H U
HU
Häring
P E
PE
Petrides
D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D005333:Fetus / Q000378:metabolism; D014644:Genetic Variation; D006031:Glycosylation; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008970:Molecular Weight; D010449:Peptide Mapping; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D019000:Phosphotyrosine; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*; D014357:Trypsin; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D003432:Cross-Linking Reagents; D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D010769:Phosphothreonine; D019000:Phosphotyrosine; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D014357:Trypsin