Proinsulin C-peptide and insulin: Limited pattern similarities of interest in inter-peptide interactions but no C-peptide effect on insulin and IGF-1 receptor signaling.
The recently reported influence of proinsulin C-peptide on insulin prompted us to examine structural features of the C-peptide. Four sets of limited pattern similarities towards inter-chain end regions of insulin were noticed, involving secondary structure elements, binding residues and intra- as well as inter-peptide residue similarities. Using surface plasmon resonance, we examined insulin binding to truncated, soluble insulin receptor A and IGF-1 receptor, but C-peptide effects on these bindings were not detectable. Two forms of the insulin receptor, differing in activation of gene transcription with regards to (pre)proinsulin and glucokinase, respectively, were also uninfluenced by C-peptide. We conclude that the pattern similarities, if functional, reflect C-peptide interactions with molecules other than both insulin A and B receptors and IGF-1 receptors. Any such effects are of interest in relation to reported binding interactions between insulin and C-peptide.
Henriksson
M
M
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden.
Johansson
J
J
Moede
T
T
Leibiger
I
I
Shafqat
J
J
Berggren
P-O
PO
Jörnvall
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001665:Binding Sites; D002096:C-Peptide / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D005941:Glucokinase / Q000235:genetics; D007328:Insulin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D011384:Proinsulin / Q000737:chemistry / Q000494:pharmacology*; D020033:Protein Isoforms; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection
D002096:C-Peptide; D007328:Insulin; D020033:Protein Isoforms; D011384:Proinsulin; D005941:Glucokinase; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin