TGF beta receptor 1

{{see also|TGF beta signaling pathway}}

The protein encoded by this gene forms a heteromeric complex with type II TGF-β receptors when bound to TGF-β, transducing the TGF-β signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys–Dietz aortic aneurysm syndrome (LDS, LDAS).{{cite web | title = Entrez Gene: TGFBR1 transforming growth factor, beta receptor I (activin A receptor type II-like kinase, 53kDa) | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7046 }}

TGF beta receptor 1 has been shown to interact with:

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• Caveolin 1,{{cite journal | vauthors = Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP | title = Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor | journal = The Journal of Biological Chemistry | volume = 276 | issue = 9 | pages = 6727–6738 | date = March 2001 | pmid = 11102446 | doi = 10.1074/jbc.M008340200 | doi-access = free }}
• Endoglin,{{cite journal | vauthors = Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C | title = Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II | journal = The Journal of Biological Chemistry | volume = 277 | issue = 32 | pages = 29197–29209 | date = August 2002 | pmid = 12015308 | doi = 10.1074/jbc.M111991200 | doi-access = free | hdl = 10261/167807 | hdl-access = free }}{{cite journal | vauthors = Barbara NP, Wrana JL, Letarte M | title = Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily | journal = The Journal of Biological Chemistry | volume = 274 | issue = 2 | pages = 584–594 | date = January 1999 | pmid = 9872992 | doi = 10.1074/jbc.274.2.584 | doi-access = free }}
• FKBP1A,{{cite journal | vauthors = Wang T, Donahoe PK, Zervos AS | title = Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12 | journal = Science | location = New York, N.Y. | volume = 265 | issue = 5172 | pages = 674–676 | date = July 1994 | pmid = 7518616 | doi = 10.1126/science.7518616 | bibcode = 1994Sci...265..674W }}{{cite journal | vauthors = Liu F, Ventura F, Doody J, Massagué J | title = Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs | journal = Molecular and Cellular Biology | volume = 15 | issue = 7 | pages = 3479–3486 | date = July 1995 | pmid = 7791754 | pmc = 230584 | doi = 10.1128/mcb.15.7.3479 }}
• FNTA,{{cite journal | vauthors = Kawabata M, Imamura T, Miyazono K, Engel ME, Moses HL | title = Interaction of the transforming growth factor-beta type I receptor with farnesyl-protein transferase-alpha | journal = The Journal of Biological Chemistry | volume = 270 | issue = 50 | pages = 29628–29631 | date = December 1995 | pmid = 8530343 | doi = 10.1074/jbc.270.50.29628 | doi-access = free }}
• Heat shock protein 90kDa alpha (cytosolic), member A1{{cite journal | vauthors = Wrighton KH, Lin X, Feng XH | title = Critical regulation of TGFbeta signaling by Hsp90 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 27 | pages = 9244–9249 | date = July 2008 | pmid = 18591668 | pmc = 2453700 | doi = 10.1073/pnas.0800163105 | bibcode = 2008PNAS..105.9244W | doi-access = free }}
• Mothers against decapentaplegic homolog 7,{{cite journal | vauthors = Mochizuki T, Miyazaki H, Hara T, Furuya T, Imamura T, Watabe T, Miyazono K | title = Roles for the MH2 domain of Smad7 in the specific inhibition of transforming growth factor-beta superfamily signaling | journal = The Journal of Biological Chemistry | volume = 279 | issue = 30 | pages = 31568–31574 | date = July 2004 | pmid = 15148321 | doi = 10.1074/jbc.M313977200 | doi-access = free }}{{cite journal | vauthors = Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K | title = Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts | journal = The Journal of Clinical Investigation | volume = 113 | issue = 2 | pages = 253–264 | date = January 2004 | pmid = 14722617 | pmc = 310747 | doi = 10.1172/JCI16269 }}{{cite journal | vauthors = Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, Ebina M, Nukiwa T, Miyazawa K, Imamura T, Miyazono K | title = Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7 | journal = The EMBO Journal | volume = 22 | issue = 24 | pages = 6458–6470 | date = December 2003 | pmid = 14657019 | pmc = 291827 | doi = 10.1093/emboj/cdg632 }}{{cite journal | vauthors = Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, Wrana JL | title = Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation | journal = Molecular Cell | volume = 6 | issue = 6 | pages = 1365–1375 | date = December 2000 | pmid = 11163210 | doi = 10.1016/s1097-2765(00)00134-9 | doi-access = free }}{{cite journal | vauthors = Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, Richardson MA, Topper JN, Gimbrone MA, Wrana JL, Falb D | title = The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling | journal = Cell | volume = 89 | issue = 7 | pages = 1165–1173 | date = June 1997 | pmid = 9215638 | doi = 10.1016/s0092-8674(00)80303-7 | s2cid = 16552782 | doi-access = free }}{{cite journal | vauthors = Datta PK, Moses HL | title = STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling | journal = Molecular and Cellular Biology | volume = 20 | issue = 9 | pages = 3157–3167 | date = May 2000 | pmid = 10757800 | pmc = 85610 | doi = 10.1128/mcb.20.9.3157-3167.2000 }}
• PPP2R2A,{{cite journal | vauthors = Griswold-Prenner I, Kamibayashi C, Maruoka EM, Mumby MC, Derynck R | title = Physical and functional interactions between type I transforming growth factor beta receptors and Balpha, a WD-40 repeat subunit of phosphatase 2A | journal = Molecular and Cellular Biology | volume = 18 | issue = 11 | pages = 6595–6604 | date = November 1998 | pmid = 9774674 | pmc = 109244 | doi = 10.1128/mcb.18.11.6595 }}
• STRAP,{{cite journal | vauthors = Datta PK, Chytil A, Gorska AE, Moses HL | title = Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling | journal = The Journal of Biological Chemistry | volume = 273 | issue = 52 | pages = 34671–34674 | date = December 1998 | pmid = 9856985 | doi = 10.1074/jbc.273.52.34671 | doi-access = free }}
• TGF beta 1,{{cite journal | vauthors = Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R | title = Determination of type I receptor specificity by the type II receptors for TGF-beta or activin | journal = Science | location = New York, N.Y. | volume = 262 | issue = 5135 | pages = 900–902 | date = November 1993 | pmid = 8235612 | doi = 10.1126/science.8235612 | bibcode = 1993Sci...262..900E }}{{cite journal | vauthors = Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E | title = Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 6 | pages = 2626–2631 | date = March 2000 | pmid = 10716993 | pmc = 15979 | doi = 10.1073/pnas.97.6.2626 | bibcode = 2000PNAS...97.2626O | doi-access = free }} and
• TGF beta receptor 2.{{cite journal | vauthors = Kawabata M, Chytil A, Moses HL | title = Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor | journal = The Journal of Biological Chemistry | volume = 270 | issue = 10 | pages = 5625–5630 | date = March 1995 | pmid = 7890683 | doi = 10.1074/jbc.270.10.5625 | doi-access = free }}

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• GW-788388
• LY-2109761
• Galunisertib (LY-2157299)
• SB-431542
• SB-525334
• RepSox{{cite journal | vauthors = Mishra T, Bhardwaj V, Ahuja N, Gadgil P, Ramdas P, Shukla S, Chande A | title = Improved loss-of-function CRISPR-Cas9 genome editing in human cells concomitant with inhibition of TGF-β signaling | journal = Molecular Therapy. Nucleic Acids | volume = 28 | pages = 202–218 | date = June 2022 | pmid = 35402072 | pmc = 8961078 | doi = 10.1016/j.omtn.2022.03.003 | s2cid = 247355285 }}

Defects are observed when the TGFBR-1 gene is either knocked-out or when a constitutively active TGFBR-1 mutant (that is active in the presence or absence of ligand) is knocked-in.

In mouse TGFBR-1 knock-out models, the female mice were sterile. They developed oviductal diverticula and defective uterine smooth muscle, meaning that uterine smooth muscle layers were poorly formed. Oviductal diverticula are small, bulging pouches located on the oviduct, which is the tube that transports the ovum from the ovary to the uterus. This deformity of the oviduct occurred bilaterally and resulted in impaired embryo development and impaired transit of the embryos to the uterus. Ovulation and fertilization still occurred in the knock-outs, however remnants of embryos were found in these oviductal diverticula.{{cite journal | vauthors = Li Q, Agno JE, Edson MA, Nagaraja AK, Nagashima T, Matzuk MM | title = Transforming growth factor β receptor type 1 is essential for female reproductive tract integrity and function | journal = PLOS Genetics | volume = 7 | issue = 10 | pages = e1002320 | date = October 2011 | pmid = 22028666 | pmc = 3197682 | doi = 10.1371/journal.pgen.1002320 | doi-access = free }}

In mouse TGFBR-1 knock-in models where a constitutively active TGFBR-1 gene is conditionally induced, the over-activation of the TGFBR-1 receptors lead to infertility, a reduction in the number of uterine glands, and hypermuscled uteri (an increased amount of smooth muscle in the uteri).{{cite journal | vauthors = Gao Y, Duran S, Lydon JP, DeMayo FJ, Burghardt RC, Bayless KJ, Bartholin L, Li Q | title = Constitutive activation of transforming growth factor Beta receptor 1 in the mouse uterus impairs uterine morphology and function | journal = Biology of Reproduction | volume = 92 | issue = 2 | pages = 34 | date = February 2015 | pmid = 25505200 | pmc = 4435420 | doi = 10.1095/biolreprod.114.125146 }}

Research into how turning off the TGFBR-1 gene affects spinal cord development in mice led to the discovery that, when the gene is turned off, external genitalia instead form as two hind legs.{{Cite journal | vauthors = Reardon S | title = Scientists made a six-legged mouse embryo — here's why | journal = Nature | date = 2024-03-28 | volume = 628 | issue = 8007 | page = 247 | pmid = 38548980 | doi = 10.1038/d41586-024-00943-7 | bibcode = 2024Natur.628..247R | url = https://www.nature.com/articles/d41586-024-00943-7 | language = en | url-access = subscription }}

These experiments show that the TGFB-1 receptor plays a critical role in the function of the female reproductive tract. They also show that genetic mutations in the TGFBR-1 gene may lead to fertility issues in women.

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• {{cite journal | vauthors = Massagué J | title = Receptors for the TGF-beta family | journal = Cell | volume = 69 | issue = 7 | pages = 1067–1070 | date = June 1992 | pmid = 1319842 | doi = 10.1016/0092-8674(92)90627-O | s2cid = 54268875 }}
• {{cite journal | vauthors = Wrana JL | title = TGF-beta receptors and signalling mechanisms | journal = Mineral and Electrolyte Metabolism | volume = 24 | issue = 2–3 | pages = 120–130 | year = 1998 | pmid = 9525694 | doi = 10.1159/000057359 | s2cid = 84458561 }}
• {{cite journal | vauthors = Josso N, di Clemente N, Gouédard L | title = Anti-Müllerian hormone and its receptors | journal = Molecular and Cellular Endocrinology | volume = 179 | issue = 1–2 | pages = 25–32 | date = June 2001 | pmid = 11420127 | doi = 10.1016/S0303-7207(01)00467-1 | s2cid = 27316217 }}

{{Refend}}

• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=taa GeneReviews/NIH/NCBI/UW entry on Thoracic Aortic Aneurysms and Aortic Dissections]
• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=loeys-dietz GeneReviews/NCBI/NIH/UW entry on Loeys-Dietz Syndrome]

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{{Cytokine receptors}}

{{Growth factor receptors}}

{{TGFβ receptor superfamily modulators}}

Category:TGF beta receptors