Follistatin (FST-344)

An endogenous secreted glycoprotein studied in preclinical models as a binding antagonist of TGF-β-superfamily ligands.

Molecular Profile

Type
Secreted glycoprotein (follistatin family; TGF-β-superfamily ligand trap)
Molecular weight
~38,007 g/mol (FST-344 precursor; UniProt P19883)
Amino acids
344
Modification
Single-chain, cysteine-rich, N-glycosylated protein organized as an N-terminal domain followed by three follistatin domains (FSD1-FSD3), each built from an EGF-like and a Kazal-like subdomain; a basic heparin-binding sequence lies within FSD1. Alternative splicing of the FST gene yields the FST-344 precursor (processed to the circulating FST-315 form) and the FST-288 isoform; FST-288 exposes the heparin-binding sequence and associates with cell-surface heparan sulfate, whereas the acidic C-terminal extension of FST-315 masks it.

Mechanism & Target Class

Follistatin functions as an extracellular ligand trap for TGF-β-superfamily ligands. Two follistatin molecules encircle a single ligand dimer (activin A/B, myostatin/GDF-8, GDF-11, and several BMPs), with the N-terminal domain occupying a type I receptor-like site and FSD1-FSD2 occluding the type II receptor site, forming a non-signaling complex. Sequestration prevents the ligands from engaging activin type II receptors (ActRIIA/ActRIIB) and the downstream SMAD2/3 pathway. The isoform-specific acidic C-terminal extension modulates exposure of the heparin-binding sequence and thereby cell-surface (heparan-sulfate) association.

Storage & Handling

Lyophilized
-20°C to -80°C, desiccated.
Handling
General handling context for a cysteine-rich glycoprotein, not a product-specific protocol; aliquot, keep sealed, and protect from repeated freeze-thaw.

Primary Database

UniProt P19883 (FST_HUMAN) ↗

References (21)

  1. Reviews

    1

    Lee SJ. (2023). Annu Rev Physiol

    DOI: 10.1146/annurev-physiol-012422-112116PubMed 36266260

  2. 2

    Cash JN, Angerman EB, Keutmann HT, Thompson TB. (2012). Mol Endocrinol

    DOI: 10.1210/me.2012-1061

  3. Clinical

    3

    Mendell JR, et al. (2017). Mol Ther

    DOI: 10.1016/j.ymthe.2017.02.015PubMed 28279643NCT01519349

  4. 4

    Greenberg SA. (2017). Mol Ther

    DOI: 10.1016/j.ymthe.2017.09.002PubMed 28927986

  5. 5

    Mendell JR, et al. (2015). Mol Ther

    DOI: 10.1038/mt.2014.200PubMed 25322757NCT01519349

  6. 6

    ClinicalTrials.gov. ClinicalTrials.gov

    NCT02354781

  7. Primary research

    7

    Pearsall RS, et al. (2019). Skeletal Muscle

    Source

  8. 8

    Shen X, et al. (2019). Sci Rep

    DOI: 10.1038/s41598-019-47818-w

  9. 9

    Cash JN, Rejon CA, McPherron AC, Bernard DJ, Thompson TB. (2009). EMBO J

    DOI: 10.1038/emboj.2009.205PubMed 19644449

  10. 10

    Kota J, et al. (2009). Sci Transl Med

    DOI: 10.1126/scitranslmed.3000112PubMed 20368179

  11. 11

    Haidet AM, et al. (2008). PNAS

    DOI: 10.1073/pnas.0709144105PubMed 18334646

  12. 12

    Lee SJ. (2007). PLoS ONE

    DOI: 10.1371/journal.pone.0000789PubMed 17726519

  13. 13

    Lerch TF, Shimasaki S, Woodruff TK, Jardetzky TS. (2007). J Biol Chem

    DOI: 10.1074/jbc.M700737200PubMed 17409095

  14. 14

    Harrington AE, et al. (2006). EMBO J

    DOI: 10.1038/sj.emboj.7601000

  15. 15

    Thompson TB, Lerch TF, Cook RW, Woodruff TK, Jardetzky TS. (2005). Dev Cell

    DOI: 10.1016/j.devcel.2005.09.008PubMed 16198295

  16. 16

    Lee SJ, McPherron AC. (2001). PNAS

    DOI: 10.1073/pnas.151270098

  17. 17

    Tsuchida K, et al. (2000). J Biol Chem

    DOI: 10.1074/jbc.M006114200PubMed 11010968

  18. 18

    Matzuk MM, Lu N, Vogel H, Sellheyer K, Roop DR, Bradley A. (1995). Nature

    DOI: 10.1038/374360a0PubMed 7885475

  19. 19

    Nakamura T, et al. (1990). Science

    DOI: 10.1126/science.2106159PubMed 2106159

  20. 20

    Shimasaki S, Koga M, Esch F, et al. (1988). PNAS

    DOI: 10.1073/pnas.85.12.4218PubMed 3380788

  21. 21

    Ueno N, Ling N, Ying SY, Esch F, Shimasaki S, Guillemin R. (1987). PNAS

    DOI: 10.1073/pnas.84.23.8282PubMed 3120188