Insulin binds to type V collagen with retention of mitogenic activity.
The abilities of eight extracellular matrix proteins, fibronectin, vitronectin, laminin, and collagen types I, II, III, IV, and V to bind insulin were examined by binding studies with insulin conjugated with peroxidase. At a physiological pH and ionic strength, type V collagen bound to insulin most strongly. The other types of collagen, laminin, and vitronectin also bound insulin with affinity lower than that of type V collagen. The insulin-binding site of type V collagen was in a 30-kDa CNBr fragment of the alpha 1 (V) chain. Analysis of the amino acid sequence showed that this 30-kDa fragment was identical to the heparin-binding fragment of type V collagen. The insulin-binding sites of laminin and vitronectin were located in the A chain and in the heparin-binding domain, respectively. Insulin bound to type V collagen stimulated the synthesis of DNA by mouse mammary tumor MTD cells, indicating that bound insulin retained mitogenic activity.
Yaoi
Y
Y
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Hashimoto
K
K
Takahara
K
K
Kato
I
I
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D007797:Laminin / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008969:Molecular Sequence Data; D013936:Thymidine / Q000378:metabolism; D019096:Vitronectin
D006023:Glycoproteins; D007328:Insulin; D007797:Laminin; D019096:Vitronectin; D006493:Heparin; D003094:Collagen; D013936:Thymidine