transforming growth factor beta-1; TGF-beta-1; contains: latency-associated peptide; LAP (TGFB1 TGFB)

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Function

multifunctional protein
controls proliferation, differentiation & other functions in many cell types
many cells synthesize TGFB1 & have specific receptors for it
positively & negatively regulates many other growth factors
role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation & differentiation in committed osteoblasts
the precursor is cleaved into mature TGF-beta-1 & latency-associated peptide (LAP_, which remains non-covalently linked to mature TGF-beta-1 rendering it inactive
the inactive form consists of a TGFB1 homodimer non-covalently linked to a latency-associated peptide (LAP)
later disulfide-linked to a latent TGFB1-binding protein anchored to the extracellular matrix
the active form is a homodimer of mature TGFB1, disulfide-linked
heterodimers of TGFB1/TGFB2 have been found in bone
interacts with CD109 & DPT
interacts with ASPN
activated in vitro at pH below 3.5 & over 12.5

homodimer, disulfide-linked
glycosylated
the 'straitjacket' & 'arm' domains encircle the growth factor monomers & are fastened together by strong bonding between Lys-56 & Tyr-103/Tyr-104
activation of TGF-beta1 requires the binding of integrin alpha-V to an RGD sequence in the prodomain & exertion of force on this domain, which is held in the extracellular matrix by latent TGF-beta binding proteins
the sheer physical force unfastens the straitjacket & releases the active growth factor dimer (putative)
belongs to the TGF-beta family

expression is increased in osteoarthritis (OA)
- co-localizes with ASPN in chondrocytes within OA lesions of articular cartilage
defects in TGFB1 are the cause of Camurati-Engelmann disease

in post-menopausal Japanese women, the frequency of Leu-10 is higher in subjects with osteoporosis than in controls