Topol LZ, Marx M, Laugier D et al (1997) Identification of drm, a novel gene whose expression is suppressed in transformed cells and which can inhibit growth of normal but not transformed cells in culture. Mol Cell Biol 17:4801–4810

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nolan K, Thompson TB (2014) The DAN family: modulators of TGF-β signaling and beyond. Protein Sci 23:999–1012. https://doi.org/10.1002/pro.2485

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kišonaitė M, Wang X, Hyvönen M (2016) Structure of Gremlin-1 and analysis of its interaction with BMP-2. Biochem J 473:1593–1604. https://doi.org/10.1042/BCJ20160254

Article  CAS  PubMed  Google Scholar 

Grillo E, Ravelli C, Corsini M et al (2016) Monomeric gremlin is a novel vascular endothelial growth factor receptor-2 antagonist. Oncotarget 7:35353–35368. https://doi.org/10.18632/oncotarget.9286

Article  PubMed  PubMed Central  Google Scholar 

Topol LZ, Bardot B, Zhang Q et al (2000) Biosynthesis, post-translation modification, and functional characterization of Drm/Gremlin *. J Biol Chem 275:8785–8793. https://doi.org/10.1074/jbc.275.12.8785

Article  CAS  PubMed  Google Scholar 

Tatsinkam AJ, Mulloy B, Rider CC (2015) Mapping the heparin-binding site of the BMP antagonist gremlin by site-directed mutagenesis based on predictive modelling. Biochem J 470:53–64. https://doi.org/10.1042/BJ20150228

Article  CAS  PubMed  Google Scholar 

Rider CC, Mulloy B (2017) Heparin, Heparan Sulphate and the TGF-β Cytokine Superfamily. Molecules 22:713. https://doi.org/10.3390/molecules22050713

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pegge J, Tatsinkam AJ, Rider CC, Bell E (2020) Heparan sulfate proteoglycans regulate BMP signalling during neural crest induction. Dev Biol 460:108–114. https://doi.org/10.1016/j.ydbio.2019.12.015

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bank, RPD RCSB PDB– 5AEJ: Crystal structure of human Gremlin-1. https://www.rcsb.org/structure/5aej. Accessed 17 Sep 2024

Katagiri T, Watabe T (2016) Bone morphogenetic proteins. Cold Spring Harb Perspect Biol 8:a021899. https://doi.org/10.1101/cshperspect.a021899

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aashaq S, Batool A, Mir SA et al (2022) TGF-β signaling: a recap of SMAD-independent and SMAD-dependent pathways. J Cell Physiol 237:59–85. https://doi.org/10.1002/jcp.30529

Article  CAS  PubMed  Google Scholar 

Maiolo D, Mitola S, Leali D et al (2012) Role of nanomechanics in canonical and noncanonical pro-angiogenic ligand/VEGF receptor-2 activation. J Am Chem Soc 134:14573–14579. https://doi.org/10.1021/ja305816p

Article  CAS  PubMed  Google Scholar 

Mitola S, Ravelli C, Moroni E et al (2010) Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2. Blood 116:3677–3680. https://doi.org/10.1182/blood-2010-06-291930

Article  CAS  PubMed  Google Scholar 

Chiodelli P, Mitola S, Ravelli C, Arteriosclerosis et al (2011) Thromb Vascular Biology 31:e116–e127. https://doi.org/10.1161/ATVBAHA.111.235184

Ravelli C, Mitola S, Corsini M, Presta M (2013) Involvement of αvβ3 integrin in gremlin-induced angiogenesis. Angiogenesis 16:235–243. https://doi.org/10.1007/s10456-012-9309-6

Article  CAS  PubMed  Google Scholar 

Mitola S, Ravelli C, Corsini M et al (2022) Production and biochemical characterization of Dimeric recombinant Gremlin-1. Int J Mol Sci 23:1151. https://doi.org/10.3390/ijms23031151

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tatsinkam AJ, Rune N, Smith J et al (2017) The binding of the bone morphogenetic protein antagonist gremlin to kidney heparan sulfate: such binding is not essential for BMP antagonism. Int J Biochem Cell Biol 83:39–46. https://doi.org/10.1016/j.biocel.2016.12.006

Article  CAS  PubMed  Google Scholar 

Rowan SC, Piouceau L, Cornwell J et al (2020) Gremlin 1 blocks vascular endothelial growth factor signaling in the pulmonary microvascular endothelium. Pulm Circ 10:2045894018807205–. https://doi.org/10.1177/2045894018807205

Article  CAS  PubMed Central  Google Scholar 

Dutton LR, O’Neill CL, Medina RJ, Brazil DP (2019) No evidence of Gremlin1-mediated activation of VEGFR2 signaling in endothelial cells. J Biol Chem 294:18041–18045. https://doi.org/10.1074/jbc.AC119.010148

Article  CAS  PubMed  PubMed Central  Google Scholar 

Müller I, Schönberger T, Schneider M et al (2013) Gremlin-1 is an inhibitor of Macrophage Migration Inhibitory factor and attenuates atherosclerotic plaque growth in ApoE–/– mice. J Biol Chem 288:31635. https://doi.org/10.1074/jbc.M113.477745

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen B, Blair DG, Plisov S et al (2004) Cutting Edge: bone morphogenetic protein antagonists Drm/Gremlin and Dan Interact with slits and Act as negative regulators of Monocyte Chemotaxis12. J Immunol 173:5914–5917. https://doi.org/10.4049/jimmunol.173.10.5914

Article  CAS  PubMed  Google Scholar 

Cheng C, Wang J, Xu P et al (2022) Gremlin1 is a therapeutically targetable FGFR1 ligand that regulates lineage plasticity and castration resistance in prostate cancer. Nat Cancer 3:565–580. https://doi.org/10.1038/s43018-022-00380-3

Article  CAS  PubMed  Google Scholar 

Park S-A, Sung NJ, Choi B-J et al (2020) Gremlin-1 augments the oestrogen-related receptor α signalling through EGFR activation: implications for the progression of breast cancer. Br J Cancer 123:988–999. https://doi.org/10.1038/s41416-020-0945-0

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ren J, Smid M, Iaria J et al (2019) Cancer-associated fibroblast-derived Gremlin 1 promotes breast cancer progression. Breast Cancer Res 21:109. https://doi.org/10.1186/s13058-019-1194-0

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kobayashi H, Gieniec KA, Wright JA et al (2021) The balance of stromal BMP signaling mediated by GREM1 and ISLR drives colorectal carcinogenesis. Gastroenterology 160:1224–1239e30. https://doi.org/10.1053/j.gastro.2020.11.011

Article  CAS  PubMed  Google Scholar 

Jang BG, Kim HS, Chang WY et al (2017) Prognostic significance of stromal GREM1 expression in colorectal cancer. Hum Pathol 62:56–65. https://doi.org/10.1016/j.humpath.2016.12.018

Article  CAS  PubMed  Google Scholar 

Gu Q, Luo Y, Chen C et al (2019) GREM1 overexpression inhibits proliferation, migration and angiogenesis of osteosarcoma. Exp Cell Res 384:111619. https://doi.org/10.1016/j.yexcr.2019.111619

Article  CAS  PubMed  Google Scholar 

Chen M-H, Yeh Y-C, Shyr Y-M et al (2013) Expression of gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors. J Gastroenterol 48:101–108. https://doi.org/10.1007/s00535-012-0614-z

Article  CAS  PubMed  Google Scholar