An anchoring protein ZFYVE9 (SARA) does not recruit SMAD2/3 to TGFB1:TGFBR2:p-TGFBR1 KD Mutants

Stable Identifier
R-HSA-3656523
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, early endosome membrane, plasma membrane
ReviewStatus
5/5
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An anchoring protein ZFYVE9 (SARA) does not recruit SMAD2/3 to TGFB1:TGFBR2:p-TGFBR1 KD Mutants
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It is assumed that TGFBR1 kinase domain (KD) mutants found in Ferguson-Smith tumor (multiple self-healing squamous epithelioma, MSSE), which have truncated KD or internal deletions in the KD (Goudie et al. 2011), cannot bind SMAD2 and SMAD3, but this has not been experimentally examined. The interaction with R-SMADs requres the presence of the L45 loop in the TGFBR1 kinase domain (amino acid residues 265-273), which is missing in some of the TGFBR1 KD truncation mutants (Chen et al. 1998). Other kinase domain regions may also be involved in the interaction with SMAD2/3 or the conformation and presentation of the L45 loop.

As TGFBR1 residues phosphorylated by TGFBR2 are upstream of kinase domain (KD) mutations that cause truncations or internal deletions in the TGFBR1 KD (Goudie et al. 2011), it is assumed that TGFBR1 KD mutants can still bind to TGF-beta (TGFB1)-activated TGFBR2 and undergo TGFBR2-mediated phosphorylation, but this has not been experimentally examined.
Literature References
PubMed ID Title Journal Year
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
9679059 Determinants of specificity in TGF-beta signal transduction

Lo, RS, Pavletich, N, Shi, Y, Hata, A, Massagué, J, Chen, YG, Wotton, D

Genes Dev. 1998
Participants
Input
Participates
as an event of
Normal reaction
An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3 (Homo sapiens)
Functional status

Loss of function of TGFB1:TGFBR2:p-TGFBR1 KD Mutants [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2013-08-08)
Akhurst, RJ  (2013-08-08)
Meyer, S  (2013-08-08)
Reviewed
Akhurst, RJ  (2013-08-08)
Meyer, S  (2013-08-08)
Created
Orlic-Milacic, M  (2013-06-05)
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