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LTBP1, LTBP3 bind TGF-Beta
Stable Identifier
R-HSA-2395328
Type
Reaction [transition]
Species
Homo sapiens
Compartment
extracellular region
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
Extracellular matrix organization (Homo sapiens)
Elastic fibre formation (Homo sapiens)
Molecules associated with elastic fibres (Homo sapiens)
LTBP1, LTBP3 bind TGF-Beta (Homo sapiens)
Signal Transduction (Homo sapiens)
Signaling by TGFB family members (Homo sapiens)
Signaling by TGF-beta Receptor Complex (Homo sapiens)
TGF-beta receptor signaling activates SMADs (Homo sapiens)
LTBP1, LTBP3 bind TGF-Beta (Homo sapiens)
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Transforming growth factor beta (TGF-beta) is a family of three cytokine ‘isoforms’ (encoded by three separate human genes) that control proliferation, cellular differentiation and other functions. TGF-beta originally referred to the founding member TGF-beta-1, now it is often used as a collective term for all three. TGF-beta is secreted from cells in latent form as part of a complex that includes two other proteins: the cleaved propeptide of TGF beta, known as latency associated peptide (LAP), and a member of the latent TGF beta binding protein (LTBP) family. LTBPs are members of the fibrillin/LTBP superfamily, characterised by the presence of unique TGF-binding protein (TB) domains, also known as 8 cys domains as they contain eight characteristic cysteines (Ramirez & Sakai 2010). LTBPs are microfibril-associated proteins that tether latent complexes of TGF-beta to microfibrils in the ECM (Taipale et al. 1996, Dallas et al. 2000, Isogai et al. 2003, Hyytiainen et al. 2004, Ono et al. 2009, Munger & Sheppard 2011). This allows TGF-beta to be targeted to the ECM where it is maintained in an inactive, latent state (Robertson et al. 2011).
LTBP1 and 3 bind all three isoforms of latent TGF-beta, while LTBP4 only weakly binds TGF-beta1 (Saharinen & Keski Oja 2000). LTBP2 does not bind TGF-beta and is a structural component of fibrillin microfibrils. The carboxyl termini of LTBP1 and LTBP4 binds to fibrillin. The incorporation of LTBP1 and LTBP4 into the ECM is abolished in fibrillin-1 null mice (Ono et al. 2009). The amino terminus of LTBPs binds ECM components such as collagen (Taipale et al. 1996) and fibronectin (Kantola et al. 2008). Fibulins compete for the LTBP sites in fibrillin (Ono et al. 2009).
Literature References
PubMed ID
Title
Journal
Year
10930463
Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta
Saharinen, J
,
Keski-Oja, J
Mol. Biol. Cell
2000
Participants
Input
x 3
LTBP1, LTBP3 [extracellular region]
(Homo sapiens)
TGFB:LAP [extracellular region]
(Homo sapiens)
Output
LTBP1,LTBP3:TGFB:LAP [extracellular region]
(Homo sapiens)
Participates
as an event of
Molecules associated with elastic fibres (Homo sapiens)
TGF-beta receptor signaling activates SMADs (Homo sapiens)
Orthologous Events
LTBP1, LTBP3 bind TGF-Beta (Bos taurus)
LTBP1, LTBP3 bind TGF-Beta (Caenorhabditis elegans)
LTBP1, LTBP3 bind TGF-Beta (Canis familiaris)
LTBP1, LTBP3 bind TGF-Beta (Gallus gallus)
LTBP1, LTBP3 bind TGF-Beta (Mus musculus)
LTBP1, LTBP3 bind TGF-Beta (Rattus norvegicus)
LTBP1, LTBP3 bind TGF-Beta (Sus scrofa)
LTBP1, LTBP3 bind TGF-Beta (Xenopus tropicalis)
Authored
Jupe, S (2012-04-30)
Reviewed
Muiznieks, LD (2012-11-02)
Created
Jupe, S (2012-06-29)
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