Other
16 Authors
- Srinivasan L,
- Tan Y,
- Neubert TA,
- Mohammadi M,
- Li Y,
- Li X,
- Cai L,
- Deng J,
- Song L,
- Zhao L,
- Niu J,
- Conklin DJ,
- Liu Y,
- Huang Z,
- Gu J,
- Lin Q
| First Author | Huang Z | Year | 2017 |
| Journal | Cell Rep | Volume | 20 |
| Issue | 7 | Pages | 1717-1728 |
| PubMed ID | 28813681 | Mgi Jnum | J:254860 |
| Mgi Id | MGI:6103940 | Doi | 10.1016/j.celrep.2017.06.063 |
| Citation | Huang Z, et al. (2017) Uncoupling the Mitogenic and Metabolic Functions of FGF1 by Tuning FGF1-FGF Receptor Dimer Stability. Cell Rep 20(7):1717-1728 |
| abstractText | The recent discovery of metabolic roles for fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the functions of this classically known mitogen. To dissect the molecular basis for this functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1(DeltaHBS)) that diminished its ability to induce heparan sulfate (HS)-assisted FGF receptor (FGFR) dimerization and activation. FGF1(DeltaHBS) exhibited a severely reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1 in vitro and in vivo. Hence, suboptimal FGFR activation by a weak FGF1-FGFR dimer is sufficient to evoke a metabolic response, whereas full FGFR activation by stable and sustained dimerization is required to elicit a mitogenic response. In addition to providing a physical basis for the diverse activities of FGF1, our findings will impact ongoing drug discoveries targeting FGF1 and related FGFs for the treatment of a variety of human diseases. |
