TGFBR2 does not recruit TGFBR1 LBD Mutants

Stable Identifier
Reaction [transition]
Homo sapiens
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Missense mutations in the ligand-binding domain (LBD) of TGF-beta receptor 1 (TGFBR1) found in Ferguson-Smith tumor i.e. mutliple self-healing squamous epithelioma (Goudie et al. 2011) and in esophageal cancer (Dulak et al. 2013) affect residues Cys41 (C41), Asn45 (N45), Gly52 (G52) and Pro83 (P83) that are all conserved between human, mouse, rat, porcine, bovine and Xenopus TGFBR1. While these TGFBR1 residues have not been identified as residues involved in interface contacts between TGFBR1 and TGF-beta 1 (TGFB1) ligand (Radaev et al. 2010), they may still allow the LBD of TGFBR1 to achieve an appropriate conformation for the interaction with TGBR2-bound TGFB1.

TGFBR1 G52R mutant was shown to be expressed on the cell surface but unresponsive to TGF-beta treatment (Goudie et al. 2011). Other LBD mutants - TGFBR1 C41Y, TGFBR1 N45S, TGFBR1 P83L and TGFBR1 P83S - have not been directly functionally studied but are assumed to behave similarly to TGFBR1 G52R.

Nonsense and frameshift mutations in the LBD of TGFBR1 that were reported in Ferguson-Smith tumor (Goudie et al. 2011) - TGFBR1 R80* and TGFBR1 N45Kfs*30 - are likely to trigger nonsense-mediated decay of mutant mRNAs, as they happen close to the 5' end of the transcript (Hagan et al. 1995). Even if they were partially translated, they could not be presented at the cell surface because they lack the transmembrane domain. These mutants are not shown here.
Literature References
PubMed ID Title Journal Year
7823948 Characterization of cis-acting sequences and decay intermediates involved in nonsense-mediated mRNA turnover

Quan, Y, Hagan, KW, Ruiz-Echevarria, MJ, Peltz, SW

Mol. Cell. Biol. 1995
21358634 Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

Gerdes, AM, Reversade, B, Lee, H, Ferguson-Smith, MA, Whittaker, S, Christie, L, Lane, EB, Nelson, SF, Broesby-Olsen, S, Avery, S, Szeverényi, I, Burrows, N, Stewart, A, Coats, SE, Merriman, B, Hayes, I, Goudie, DR, Friedel, J, D'Alessandro, M, O'Connor, BD, Pichert, G, Lunny, DP, Verma, C

Nat. Genet. 2011
23525077 Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity

Luketich, JD, Ogino, S, Pennathur, A, Imamura, Y, Stewart, C, Voet, D, Stojanov, P, Lin, J, Onofrio, RC, Bass, AJ, Beer, DG, McKenna, A, Reddy, R, Gabriel, SB, Sougnez, C, Landrenau, R, Lin, L, Lander, ES, Thompson, K, Ramos, AH, Golub, TR, Carter, SL, Zhou, Z, Dulak, AM, Schumacher, SE, Bandla, S, Sivachenko, A, Saksena, G, Godfrey, TE, Beroukhim, R, Guiducci, C, Getz, G, Auclair, D, Lawrence, MS, Peng, S, Chang, A, Shefler, E, Cibulskis, K, Fox, C

Nat. Genet. 2013
20207738 Ternary complex of transforming growth factor-beta1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily

Sun, PD, Lafer, EM, Hinck, AP, Radaev, S, Zou, Z, Huang, T

J. Biol. Chem. 2010
Normal reaction
Functional status

Loss of function of TGFBR1 LBD Mutants:FKBP1A [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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