Massague J. TGFb signalling in context. Nat Rev Mol Cell Biol. 2012;13(10):616–30.
Article
CAS
PubMed
PubMed Central
Google Scholar
Davis H, Raja E, Miyazono K, Tsubakihara Y, Moustakas A. Mechanisms of action of bone morphogenetic proteins in cancer. Cytokine Growth Factor Rev. 2016;27:81–92.
Article
CAS
PubMed
Google Scholar
Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol. 1998;16(3):247–52.
Article
CAS
PubMed
Google Scholar
Han HQ, Zhou X, Mitch WE, Goldberg AL. Myostatin/activin pathway antagonism: molecular basis and therapeutic potential. Int J Biochem Cell Biol. 2013;45(10):2333–47.
Article
CAS
PubMed
Google Scholar
Parvani JG, Taylor MA, Schiemann WP. Noncanonical TGF-b signaling during mammary tumorigenesis. J Mammary Gland Biol Neoplasia. 2011;16(2):127–46.
Article
PubMed
PubMed Central
Google Scholar
Morikawa M, Derynck R, Miyazono K. TGF-b and the TGF-b Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harb Perspect Biol. 2016;8(5):a021873.
Article
PubMed
PubMed Central
Google Scholar
Allen RS, Tajer B, Shore EM, Mullins MC. Fibrodysplasia ossificans progressiva mutant ACVR1 signals by multiple modalities in the developing zebrafish. eLife. 2020;9:e53761.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ehrlich M, Gutman O, Knaus P, Henis YI. Oligomeric interactions of TGF-b and BMP receptors. FEBS Lett. 2012;586(14):1885–96.
Article
CAS
PubMed
Google Scholar
Goebel EJ, Corpina RA, Hinck CS, Czepnik M, Castonguay R, Grenha R, et al. Structural characterization of an activin class ternary receptor complex reveals a third paradigm for receptor specificity. Proc Natl Acad Sci U S A. 2019;116(31):15505–13.
Article
CAS
PubMed
PubMed Central
Google Scholar
Moustakas A, Heldin CH. Non-Smad TGF-b signals. J Cell Sci. 2005;118(Pt 16):3573–84.
Article
CAS
PubMed
Google Scholar
Yamashita M, Fatyol K, Jin C, Wang X, Liu Z, Zhang YE. TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-b. Mol Cell. 2008;31(6):918–24.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sieber C, Kopf J, Hiepen C, Knaus P. Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev. 2009;20(5-6):343–55.
Article
CAS
PubMed
Google Scholar
Bauer J, Ozden O, Akagi N, Carroll T, Principe DR, Staudacher JJ, et al. Activin and TGFb use diverging mitogenic signaling in advanced colon cancer. Mol Cancer. 2015;14:182.
Article
PubMed
PubMed Central
Google Scholar
Heldin CH, Moustakas A. Role of Smads in TGFb signaling. Cell Tissue Res. 2012;347(1):21–36.
Article
CAS
PubMed
Google Scholar
Budi EH, Duan D, Derynck R. Transforming growth factor-b receptors and Smads: Regulatory complexity and functional versatility. Trends Cell Biol. 2017;27(9):658–72.
Article
CAS
PubMed
Google Scholar
Yadin D, Knaus P, Mueller TD. Structural insights into BMP receptors: Specificity, activation and inhibition. Cytokine Growth Factor Rev. 2016;27:13–34.
Article
CAS
PubMed
Google Scholar
Shi Y, Massague J. Mechanisms of TGF-b signaling from cell membrane to the nucleus. Cell. 2003;113(6):685–700.
Article
CAS
PubMed
Google Scholar
Lebrin F, Deckers M, Bertolino P, Ten Dijke P. TGF-b receptor function in the endothelium. Cardiovasc Res. 2005;65(3):599–608.
Article
CAS
PubMed
Google Scholar
Moustakas A, Heldin CH. The regulation of TGFb signal transduction. Development. 2009;136(22):3699–714.
Article
CAS
PubMed
Google Scholar
Hino K, Ikeya M, Horigome K, Matsumoto Y, Ebise H, Nishio M, et al. Neofunction of ACVR1 in fibrodysplasia ossificans progressiva. Proc Natl Acad Sci U S A. 2015;112(50):15438–43.
Article
CAS
PubMed
PubMed Central
Google Scholar
Olsen OE, Sankar M, Elsaadi S, Hella H, Buene G, Darvekar SR, et al. BMPR2 inhibits activin and BMP signaling via wild-type ALK2. J Cell Sci. 2018;131(11):jcs213512.
Article
PubMed
Google Scholar
Holtzhausen A, Golzio C, How T, Lee YH, Schiemann WP, Katsanis N, et al. Novel bone morphogenetic protein signaling through Smad2 and Smad3 to regulate cancer progression and development. FASEB J. 2014;28(3):1248–67.
Article
CAS
PubMed
PubMed Central
Google Scholar
Star GP, Giovinazzo M, Langleben D. Bone morphogenic protein-9 stimulates endothelin-1 release from human pulmonary microvascular endothelial cells: a potential mechanism for elevated ET-1 levels in pulmonary arterial hypertension. Microvasc Res. 2010;80(3):349–54.
Article
CAS
PubMed
Google Scholar
Upton PD, Davies RJ, Trembath RC, Morrell NW. Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells. J Biol Chem. 2009;284(23):15794–804.
Article
CAS
PubMed
PubMed Central
Google Scholar
Haupt J, Xu M, Shore EM. Variable signaling activity by FOP ACVR1 mutations. Bone. 2018;109:232–40.
Article
CAS
PubMed
Google Scholar
Caja L, Tzavlaki K, Dadras MS, Tan EJ, Hatem G, Maturi NP, et al. Snail regulates BMP and TGFb pathways to control the differentiation status of glioma-initiating cells. Oncogene. 2018;37(19):2515–31.
Article
CAS
PubMed
PubMed Central
Google Scholar
Olsen OE, Wader KF, Hella H, Mylin AK, Turesson I, Nesthus I, et al. Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B. Cell Commun Signal. 2015;13:27.
Article
PubMed
PubMed Central
Google Scholar
Martinez-Hackert E, Sundan A, Holien T. Receptor binding competition: A paradigm for regulating TGF-b family action. Cytokine Growth Factor Rev. 2021;57:39–54.
Article
CAS
PubMed
Google Scholar
Aykul S, Moust J, Floer M, Martinez-Hackert E. TGF-β family inhibitors blunt adipogenesis via non-canonical regulation of SMAD pathways. bioRxiv. 2020; https://doi.org/10.1101/2020.03.12.988568.
Meier D, Lodberg A, Gvozdenovic A, Pellegrini G, Neklyudova O, Born W, et al. Inhibition of the activin receptor signaling pathway: A novel intervention against osteosarcoma. Cancer Med. 2021;10(1):286–96.
Article
CAS
PubMed
Google Scholar
Zhu J, Liu F, Wu Q, Liu X. Activin A regulates proliferation, invasion and migration in osteosarcoma cells. Mol Med Rep. 2015;11(6):4501–7.
Article
CAS
PubMed
Google Scholar
Tian H, Zhou T, Chen H, Li C, Jiang Z, Lao L, et al. Bone morphogenetic protein-2 promotes osteosarcoma growth by promoting epithelial-mesenchymal transition (EMT) through the Wnt/beta-catenin signaling pathway. J Orthop Res. 2019;37(7):1638–48.
Article
CAS
PubMed
Google Scholar
Verrecchia F, Redini F. Transforming growth factor-b signaling plays a pivotal role in the interplay between osteosarcoma cells and their microenvironment. Front Oncol. 2018;8:133.
Article
PubMed
PubMed Central
Google Scholar
Feng XH, Derynck R. Specificity and versatility in TGF-b signaling through Smads. Annu Rev Cell Dev Biol. 2005;21:659–93.
Article
CAS
PubMed
Google Scholar
Townson SA, Martinez-Hackert E, Greppi C, Lowden P, Sako D, Liu J, et al. Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex. J Biol Chem. 2012;287(33):27313–25.
Article
CAS
PubMed
PubMed Central
Google Scholar
Antebi YE, Linton JM, Klumpe H, Bintu B, Gong M, Su C, et al. Combinatorial Signal Perception in the BMP Pathway. Cell. 2017;170(6):1184–96 e24.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lowery JW, Intini G, Gamer L, Lotinun S, Salazar VS, Ote S, et al. Loss of BMPR2 leads to high bone mass due to increased osteoblast activity. J Cell Sci. 2015;128(7):1308–15.
Article
CAS
PubMed
PubMed Central
Google Scholar
Olsen OE, Hella H, Elsaadi S, Jacobi C, Martinez-Hackert E, Holien T. Activins as dual specificity TGF-b family molecules: SMAD-Activation via Activin- and BMP-Type 1 Receptors. Biomolecules. 2020;10(4):519.
Article
CAS
PubMed Central
Google Scholar
Aykul S, Corpina RA, Goebel EJ, Cunanan CJ, Dimitriou A, Kim HJ, et al. Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop. eLife. 2020;9:e54582.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gilboa L, Wells RG, Lodish HF, Henis YI. Oligomeric structure of type I and type II TGF-b receptors: homo-dimers form in the ER and persist at the plasma membrane. J Cell Biol. 1998;140(4):767–70.
Article
CAS
PubMed
PubMed Central
Google Scholar
Henis YI, Moustakas A, Lin HY, Lodish HF. The types II and III transforming growth factor-b receptors form homo-oligomers. J Cell Biol. 1994;126(1):139–54.
Article
CAS
PubMed
Google Scholar
Rechtman MM, Nakaryakov A, Shapira KE, Ehrlich M, Henis YI. Different domains regulate homomeric and heteromeric complex formation among type I and type II transforming growth factor-b receptors. J Biol Chem. 2009;284(12):7843–52.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wells RG, Gilboa L, Sun Y, Liu X, Henis YI, Lodish HF. Transforming growth factor-b induces formation of a dithiothreitol-resistant type I/Type II receptor complex in live cells. J Biol Chem. 1999;274(9):5716–22.
Article
CAS
PubMed
Google Scholar
Gilboa L, Nohe A, Geissendorfer T, Sebald W, Henis YI, Knaus P. Bone morphogenetic protein receptor complexes on the surface of live cells: A new oligomerization mode for Serine/Threonine kinase receptors. Mol Biol Cell. 2000;11(3):1023–35.
Article
CAS
PubMed
PubMed Central
Google Scholar
Marom B, Heining E, Knaus P, Henis YI. Formation of stable homomeric and transient heteromeric bone morphogenetic protein (BMP) receptor complexes regulates Smad protein signaling. J Biol Chem. 2011;286(22):19287–96.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nohe A, Hassel S, Ehrlich M, Neubauer F, Sebald W, Henis YI, et al. The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J Biol Chem. 2002;277(7):5330–8.
Article
CAS
PubMed
Google Scholar
Groppe J, Hinck CS, Samavarchi-Tehrani P, Zubieta C, Schuermann JP, Taylor AB, et al. Cooperative assembly of TGF-b superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding. Mol Cell. 2008;29(2):157–68.
Article
CAS
PubMed
Google Scholar
Radaev S, Zou Z, Huang T, Lafer EM, Hinck AP, Sun PD. Ternary complex of transforming growth factor-b1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily. J Biol Chem. 2010;285(19):14806–14.
Article
CAS
PubMed
PubMed Central
Google Scholar
Allendorph GP, Vale WW, Choe S. Structure of the ternary signaling complex of a TGF-b superfamily member. Proc Natl Acad Sci U S A. 2006;103(20):7643–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Weber D, Kotzsch A, Nickel J, Harth S, Seher A, Mueller U, et al. A silent H-bond can be mutationally activated for high-affinity interaction of BMP-2 and activin type IIB receptor. BMC Struct Biol. 2007;7:6.
Article
PubMed
PubMed Central
Google Scholar
Agnew C, Ayaz P, Kashima R, Loving HS, Ghatpande P, Kung JE, et al. Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization. Nat Commun. 2021;12(1):4950.
Article
CAS
PubMed
PubMed Central
Google Scholar
Risbridger GP, Schmitt JF, Robertson DM. Activins and inhibins in endocrine and other tumors. Endocr Rev. 2001;22(6):836–58.
Article
CAS
PubMed
Google Scholar
Fields SZ, Parshad S, Anne M, Raftopoulos H, Alexander MJ, Sherman ML, et al. Activin receptor antagonists for cancer-related anemia and bone disease. Expert Opin Investig Drugs. 2013;22(1):87–101.
Article
CAS
PubMed
Google Scholar
Antsiferova M, Huber M, Meyer M, Piwko-Czuchra A, Ramadan T, MacLeod AS, et al. Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response. Nat Commun. 2011;2:576.
Article
PubMed
Google Scholar
Leto G. Activin A and bone metastasis. J Cell Physiol. 2010;225(2):302–9.
Article
CAS
PubMed
Google Scholar
Petersen NO, Felder S, Elson EL. Measurement of lateral diffusion by fluorescence photobleaching recovery. In: Weir DM, Herzenberg LA, Blackwell CC, Herzenberg LA, editors. Handbook of Experimental Immunology. Edinburgh: Blackwell Scientific Publications; 1986. p. 24.1-24.3.
Google Scholar
Yao D, Ehrlich M, Henis YI, Leof EB. Transforming growth factor-b receptors interact with AP2 by direct binding to b2 subunit. Mol Biol Cell. 2002;13(11):4001–12.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tazat K, Hector-Greene M, Blobe GC, Henis YI. TbRIII independently binds type I and type II TGF-b receptors to inhibit TGF-b signaling. Mol Biol Cell. 2015;26(19):3535–45.
Article
CAS
PubMed
PubMed Central
Google Scholar
Pomeraniec L, Hector-Greene M, Ehrlich M, Blobe GC, Henis YI. Regulation of TGF-b receptor hetero-oligomerization and signaling by endoglin. Mol Biol Cell. 2015;26(17):3117–27.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tazat K, Pomeraniec-Abudy L, Hector-Greene M, Szilagyi SS, Sharma S, Cai EM, et al. ALK1 Regulates the Internalization of Endoglin and the type III TGF-b Receptor. Mol Biol Cell. 2021;32(7):605–21.
Article
CAS
PubMed
PubMed Central
Google Scholar
Henis YI, Katzir Z, Shia MA, Lodish HF. Oligomeric structure of the human asialoglycoprotein receptor: nature and stoichiometry of mutual complexes containing H1 and H2 polypeptides assessed by fluorescence photobleaching recovery. J Cell Biol. 1990;111(4):1409–18.
Article
CAS
PubMed
Google Scholar
Eisenberg S, Shvartsman DE, Ehrlich M, Henis YI. Clustering of raft-associated proteins in the external membrane leaflet modulates internal leaflet H-Ras diffusion and signaling. Mol Cell Biol. 2006;26(19):7190–200.
Article
CAS
PubMed
PubMed Central
Google Scholar
Mura M, Cappato S, Giacopelli F, Ravazzolo R, Bocciardi R. The role of the 3'UTR region in the regulation of the ACVR1/Alk-2 gene expression. PLoS One. 2012;7(12):e50958.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang S, Ren T, Jiao G, Huang Y, Bao X, Zhang F, et al. BMPR2 promotes invasion and metastasis via the RhoA-ROCK-LIMK2 pathway in human osteosarcoma cells. Oncotarget. 2017;8(35):58625–41.
Article
PubMed
PubMed Central
Google Scholar
Ghandi M, Huang FW, Jane-Valbuena J, Kryukov GV, Lo CC, McDonald ER 3rd, et al. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019;569(7757):503–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401–4.
Article
Google Scholar
Mohedas AH, Xing X, Armstrong KA, Bullock AN, Cuny GD, Yu PB. Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS Chem Biol. 2013;8(6):1291–302.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hartung A, Bitton-Worms K, Rechtman MM, Wenzel V, Borgermann JH, Hassel S, et al. Different routes of BMP receptor endocytosis influence BMP signaling. Mol Cell Biol. 2006;26(20):7791–805.
Article
CAS
PubMed
PubMed Central
Google Scholar
Guzman A, Zelman-Femiak M, Boergermann JH, Paschkowsky S, Kreuzaler PA, Fratzl P, et al. SMAD versus non-SMAD signaling is determined by lateral mobility of bone morphogenetic protein (BMP) receptors. J Biol Chem. 2012;287(47):39492–504.
Article
CAS
PubMed
PubMed Central
Google Scholar
Saffman PG, Delbruck M. Brownian motion in biological membranes. Proc Natl Acad Sci U S A. 1975;72:3111–3.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sheetz MP, Schindler M, Koppel DE. Lateral mobility of integral membrane proteins is increased in spherocytic erythrocytes. Nature. 1980;285(5765):510–1.
Article
CAS
PubMed
Google Scholar
Jacobson K, Ishihara A, Inman R. Lateral diffusion of proteins in membranes. Annu Rev Physiol. 1987;49:163–75.
Article
CAS
PubMed
Google Scholar
Sako Y, Kusumi A. Barriers for lateral diffusion of transferrin receptor in the plasma membrane as characterized by receptor dragging by laser tweezers: fence versus tether. J Cell Biol. 1995;129(6):1559–74.
Article
CAS
PubMed
Google Scholar
Fire E, Gutman O, Roth MG, Henis YI. Dynamic or stable interactions of influenza hemagglutinin mutants with coated pits. Dependence on the internalization signal but not on aggregation. J Biol Chem. 1995;270(36):21075–81.
Article
CAS
PubMed
Google Scholar
Tajer B, Dutko JA, Little SC, Mullins MC. BMP heterodimers signal via distinct type I receptor class functions. Proc Natl Acad Sci U S A. 2021;118(15):e2017952118.
Article
CAS
PubMed
PubMed Central
Google Scholar
Evan GI, Lewis GK, Ramsay G, Bishop JM. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985;5(12):3610–6.
CAS
PubMed
PubMed Central
Google Scholar
Shapira KE, Gross A, Ehrlich M, Henis YI. Coated pit-mediated endocytosis of the type I transforming growth factor-b (TGF-b) receptor depends on a di-leucine family signal and is not required for signaling. J Biol Chem. 2012;287(32):26876–89.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kfir S, Ehrlich M, Goldshmid A, Liu X, Kloog Y, Henis YI. Pathway- and expression level-dependent effects of oncogenic N-Ras: p27Kip1 mislocalization by the Ral-GEF pathway and Erk-mediated interference with Smad signaling. Mol Cell Biol. 2005;25(18):8239–50.
Article
CAS
PubMed
PubMed Central
Google Scholar
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-DDCT Method. Methods. 2001;25(4):402–8.
Article
CAS
PubMed
Google Scholar