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2016 ; 11
(3
): e0150453
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Potency of Full-Length MGF to Induce Maximal Activation of the IGF-I R Is Similar
to Recombinant Human IGF-I at High Equimolar Concentrations
#MMPMID26991004
Janssen JA
; Hofland LJ
; Strasburger CJ
; van den Dungen ES
; Thevis M
PLoS One
2016[]; 11
(3
): e0150453
PMID26991004
show ga
AIMS: To compare full-length mechano growth factor (full-length MGF) with human
recombinant insulin-like growth factor-I (IGF-I) and human recombinant insulin
(HI) in their ability to activate the human IGF-I receptor (IGF-IR), the human
insulin receptor (IR-A) and the human insulin receptor-B (IR-B), respectively. In
addition, we tested the stimulatory activity of human MGF and its stabilized
analog Goldspink-MGF on the IGF-IR. METHODS: The effects of full-length MGF,
IGF-I, human mechano growth factor (MGF), Goldspink-MGF and HI were compared
using kinase specific receptor activation (KIRA) bioassays specific for IGF-I,
IR-A or IR-B, respectively. These assays quantify activity by measuring
auto-phosphorylation of the receptor upon ligand binding. RESULTS: IGF-IR: At
high equimolar concentrations maximal IGF-IR stimulating effects generated by
full-length MGF were similar to that of IGF-I (89-fold vs. 77-fold,
respectively). However, EC50 values of IGF-I and full-length MGF for the IGF-I
receptor were 0.86 nmol/L (95% CI 0.69-1.07) and 7.83 nmol/L (95% CI:
4.87-12.58), respectively. No IGF-IR activation was observed by human MGF and
Goldspink-MGF, respectively. IR-A/IR-B: At high equimolar concentrations similar
maximal IR-A stimulating effects were observed for full -length MGF and HI, but
maximal IR-B stimulation achieved by full -length MGF was stronger than that by
HI (292-fold vs. 98-fold). EC50 values of HI and full-length MGF for the IR-A
were 1.13 nmol/L (95% CI 0.69-1.84) and 73.11 nmol/L (42.87-124.69),
respectively; for IR-B these values were 1.28 nmol/L (95% CI 0.64-2.57) and 35.10
nmol/L (95% 17.52-70.33), respectively. CONCLUSIONS: Full-length MGF directly
stimulates the IGF-IR. Despite a higher EC50 concentration, at high equimolar
concentrations full-length MGF showed a similar maximal potency to activate the
IGF-IR as compared to IGF-I. Further research is needed to understand the actions
of full-length MGF in vivo and to define the physiological relevance of our in
vitro findings.