[Leu27] insulin-like growth factor II is highly selective for the type-II IGF receptor in binding, cross-linking and thymidine incorporation experiments.
Insulin-like growth factor-II (IGF-II) is able to interact with three different receptors: the type-I and type-II IGF receptors, and the insulin receptor, although with a lower affinity. This cross reactivity obscures the mechanisms via which the biological activities of IGF-II are mediated. We have synthesized an IGF-II analog, [Leu27]IGF-II, that is highly selective for the type-II IGF receptor. Receptor binding experiments demonstrate a high affinity for the type-II IGF receptor, analogous to synthetic (syn) and recombinant (rec) IGF-II, but no affinity for the type-I IGF and the insulin receptor at concentrations up to 50 and 200 ng/ml, respectively. The lack of affinity for these two receptors is confirmed by biological studies which demonstrated that this analog, in contrast with synIGF-II, did not stimulate [3H]thymidine incorporation in Balb/c 3T3 cells. [Leu27]IGF-II opens new ways to identify which actions of IGF-II are mediated via the type-II receptor and which are due to cross reactivity with the type-I IGF or the insulin receptor.
Beukers
M W
MW
Department of Pediatrics, Stanford University Medical Center, CA 94305.
Oh
Y
Y
Zhang
H
H
Ling
N
N
Rosenfeld
R G
RG
D000818:Animals; D001667:Binding, Competitive; D003432:Cross-Linking Reagents; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000031:analogs & derivatives* / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010920:Placenta / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism*
D003432:Cross-Linking Reagents; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; C067045:insulin-like growth factor II, Leu(27)-; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin; D013936:Thymidine