Regulation of the mannose 6-phosphate/IGF II receptor expression at the cell surface by mannose 6-phosphate, insulin like growth factors and epidermal growth factor.
Mannose 6-phosphate, insulin like growth factors I and II (IGF I, IGF II), insulin and epidermal growth factor (EGF) induce a 1.5- to 2-fold increase of mannose 6-phosphate binding sites at the cell surface of human skin fibroblasts. The increase is completed within 10-15 min, is dose and temperature dependent, reversible and transient even in the presence of the effectors. It is due to a redistribution of mannose 6-phosphate/IGF II receptors from internal membranes to the cell surface, while the affinity of the receptors is not affected. Combinations of mannose 6-phosphate with IGF I, IGF II or EGF stimulate the redistribution of the receptor to the cell surface in an additive manner, while combinations of the growth factors result in a non-additive stimulation of redistribution. The redistribution is not dependent on extracellular calcium and appears also to be independent of changes of free intracellular calcium. Pre-treatment of fibroblasts with cholera toxin or pertussis toxin increases the number of cell surface receptors 2- and 1.5-fold, respectively. Neither of the toxins affects the redistribution of mannose 6-phosphate/IGF II receptors induced by the growth factors, while both toxins abolish the receptor redistribution induced by mannose 6-phosphate. These results suggest a multiple regulation of the cell surface expression of mannose 6-phosphate/IGF II receptors by Gs- and Gi-like proteins sensitive to cholera toxin and pertussis toxin and by stimulation of mannose 6-phosphate/IGF II, IGF I and EGF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Braulke
T
T
Georg-August-Universität Göttingen Abt. Biochemie II, FRG.
Tippmer
S
S
Neher
E
E
von Figura
K
K
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008360:Mannosephosphates / Q000494:pharmacology; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017451:Receptors, Somatomedin; D015398:Signal Transduction
D007328:Insulin; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; C027693:mannose-6-phosphate; D004815:Epidermal Growth Factor; D007335:Insulin-Like Growth Factor II; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D002118:Calcium