Interactions of recombinant and platelet transforming growth factor-beta 1 precursor with the insulin-like growth factor II/mannose 6-phosphate receptor.
Recombinant transforming growth factor (TGF)-beta 1 precursor was recently found to contain mannose 6-phosphate (Purchio et al., 1988, J. Biol. Chem. 263, 14211-14215). In the present study, recombinant TGF-beta 1 precursor was shown to bind to the insulin-like growth factor (IGF)-II/mannose 6-phosphate (man6P) receptor on the plasma membrane of cells since: 1) Insulin, which induces an increase in cell surface IGF-II/man6P receptors on adipocytes, caused a 2.7-fold increase in TGF-beta 1 precursor binding to adipocytes; 2) Chinese hamster ovary cells selected for overexpression of the IGF-II/man6P receptor exhibited an increased binding of TGF-beta 1 precursor in comparison to the parental cells; and 3) the binding of 125I-TGF-beta 1 precursor to these transfected cells and adipocytes was largely inhibited by man6P. After 15 minutes at 37 degrees C, 75% of the recombinant TGF-beta 1 precursor was found to be internalized in the transfected cells. Additional studies with latent TGF-beta 1 isolated from platelets indicated that this material could also bind to the isolated IGF-II/man6P receptor.
Kovacina
K S
KS
Department of Pharmacology, Stanford University School of Medicine, CA 94305-5332.
Steele-Perkins
G
G
Purchio
A F
AF
Lioubin
M
M
Miyazono
K
K
Heldin
C H
CH
Roth
R A
RA
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000032:analysis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000235:genetics; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008360:Mannosephosphates / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D014162:Transfection; D015291:Transforming Growth Factors / Q000378:metabolism*
D007328:Insulin; D008360:Mannosephosphates; D011498:Protein Precursors; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; C027693:mannose-6-phosphate; D015291:Transforming Growth Factors; D004247:DNA