Human Transforming Growth Factor-Beta 3 (TGFB3)

Specification

• Cat#: THP-0244
• Product Name: Human Transforming Growth Factor-Beta 3 (TGFB3)
• Description: TGF­beta 3 (transforming growth factor-beta 3) is a member of a TGF­-beta superfamily subgroup that is defined by their structural and functional similarities.
• Species: Human
• Molecular Weight: Predicted Molecular Mass: 12.7 kDa (monomer). SDS-PAGE: 12 kDa, reducing conditions; 24 kDa, non-reducing conditions.
• Source: Baculovirus infected Sf21 cells
• Introduction: TGF-beta 3 and its closely related proteins, TGF-beta 1 and ­-beta 2, act as cellular switches to regulate immune function, cell proliferation, and epithelial­-mesenchymal transition. The non-redundant biological effects of TGF-­ beta 3 include involvement in palatogenesis, chondrogenesis, and pulmonary development. Human TGF-­ beta 3 cDNA encodes a 412 amino acid (aa) precursor that contains a 20 aa signal peptide and a 392 aa proprotein. The proprotein is processed by a furin­like convertase to generate a 220 aa latency­associated peptide (LAP) and a 112 aa mature TGF­-beta 3. Mature human TGF­-beta 3 shows 100%, 99%, and 98% aa identity with mouse/dog/horse, rat, and pig TGF-­ beta 3, respectively. TGF-beta 3 is secreted as a complex with LAP. This latent form of TGF-beta 3 becomes active upon cleavage by plasmin, matrix metalloproteases, thrombospondin-1, and a subset of integrins. TGF-beta 3 binds with high affinity to TGF-beta RII, a type II serine/threonine kinase receptor. This receptor then phosphorylates and activates type I serine/threonine kinase receptors, TGF-­ beta RI or ALK-­1, to modulate transcription through Smad phosphorylation. The divergent biological effects exerted by individual TGF-beta isoforms is dependent upon the recruitment of co-receptors (TGF-­ beta RIII and endoglin) and the subsequent initiation of Smad-­dependent or -independent signaling pathways.
• Purity: >97%, by SDS-PAGE under reducing conditions and visualized by silver stain.
• Formulation: Lyophilized from a 0.2 μm filtered solution in Acetonitrile and TFA with BSA as a carrier protein.
• Biological Activity: Measured by its ability to inhibit the IL-4-dependent proliferation of HT‑2 mouse T cells. Tsang, M. et al. (1995) Cytokine 7:389. The ED50 for this effect is 0.01-0.04 ng/mL. The specific activity of recombinant human TGF-beta 3 is approximately 2.2 x 104 IU/μg, which is calibrated against recombinant human TGF-beta 3 WHO International Standard (NIBSC code: 09/234).
• Reconstitution: Reconstitute at 20 μg/mL in sterile 4 mM HCl containing 1 mg/mL human or bovine serum albumin.

Pharmaceutical Information

• Applications: The non-redundant biological effects of TGF-­ beta 3 include involvement in palatogenesis, chondrogenesis, and pulmonary development.
• Examples of Clinical Use: Promoting palatogenesis, chondrogenesis, and pulmonary development
• Affected organisms: Humans

Related Reading

Structure of TGFB3

TGFB3 encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. This protein is involved in embryogenesis and cell differentiation, and may play a role in wound healing. Mutations in this gene are a cause of aortic aneurysms and dissections, as well as familial arrhythmogenic right ventricular dysplasia 1. Gene Ontology (GO) annotations related to this gene include identical protein binding and cytokine activity. An important paralog of this gene is TGFB2.

Three dimensional structures for TGFB3 Gene

Function of TGFB3

TGFB3 is the precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively.

The gene is required to maintain the Transforming growth factor beta-3 (TGF-beta-3) chain in a latent state during storage in extracellular matrix. TGFB3 associates non-covalently with TGF-beta-3 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-3. Its interaction with integrins results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-3.

TGFB3 is a multifunctional protein that regulates embryogenesis and cell differentiation and is required in various processes such as secondary palate development. Following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains remain non-covalently linked rendering TGF-beta-3 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP that control activation of TGF-beta-3 and maintain it in a latent state during storage in extracellular milieus.

Integrin-binding results in distortion of the LAP chain and subsequent release of the active TGF-beta-3. Once it is activated following release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal.

Diseases associated with TGFB3 include Loeys-Dietz Syndrome 5 and Arrhythmogenic Right Ventricular Dysplasia, Familial, 1. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and MIF Mediated Glucocorticoid Regulation.

TGFB3 Related Pathways

There are 76 pathways. Here are some of them.

14-3-3 Induced Intracellular Signaling Actin-Based Motility by Rho Family GTPases
Activation of cAMP-Dependent PKA
Activation of PKA through GPCR
Activation of PKC through GPCR
Akt Signaling
all-trans-Retinoic Acid Signaling in Brain
Antioxidant Action of Vitamin-C
Apoptotic Pathways in Synovial Fibroblasts
Breast Cancer Regulation by Stathmin1
cAMP Pathway
Cellular Apoptosis Pathway
Colorectal Cancer Metastasis
Inhibition of Angiogenesis by TSP1
Intracellular Calcium Signaling
IP3 Pathway
JAK-STAT Pathway
JNK Pathway
MAPK Family Pathway
MAPK Signaling
MIF Mediated Glucocorticoid Regulation
MIF Regulation of Innate Immune Cells
Mitochondrial Apoptosis
Mitotic Roles of Polo Like Kinases
Molecular Mechanisms of Cancer
mTOR Pathway
Nanog in Mammalian ESC Pluripotency
NFAT in Immune Response
NF-KappaB (p50-p65) Pathway
NF-KappaB Family Pathway
Nuclear Receptor Activation by Vitamin-A

TGFB3 Related Drugs

About TGFB3, there are 23 pipelines under study, 12 of which have been approved.

Fresolimumab(investigational) has been used in trials studying the treatment of Primary Brain Tumors, Metastatic Breast Cancer, Diffuse Systemic Sclerosis, Pleural Malignant Mesothelioma, and Primary Focal Segmental Glomerulosclerosis.

Dexamethasone is a glucocorticoid available in various modes of administration that is used for the treatment of various inflammatory conditions, including bronchial asthma, as well as endocrine and rheumatic disorders.

Dopamine is a catecholamine neurotransmitter used to treat hemodynamic imbalances, poor perfusion of vital organs, low cardiac output, and hypotension.

Nitric Oxide is a vasodilating agent used in the treatment of hypoxic respiratory failure in premature neonates.

Progesterone is a hormone used for a variety of functions, including contraception, control of abnormal uterine bleeding, maintenance of pregnancy, and prevention of endometrial hyperplasia.

Raloxifene is a selective estrogen receptor modulator that is used to prevent and treat osteoporosis and reduce the risk of invasive breast cancer in high-risk postmenopausal women.