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TGF-beta 1 - a versatile signaling molecule with roles in development and disease

Wed, 06/10/2015 - 14:52


The transforming growth factor-β (TGF-beta) family consists of a wide variety of signaling proteins with roles in development. TGF-beta signaling controls growth, differentiation, and immune responses and is often misregulated in cancer. TGF-beta 1 is the most widely expressed and abundant isoform of the TGF-beta family. TGF-beta proteins signal through two classes of receptors: type I (TβRI) and type II (TβRI). These receptor proteins are serine threonine kinases found at the cell surface. Binding of TGF-beta induces the formation of a heterocomplex with TβRI and TβRII and leads to the phosphorylation of TβRI by TβRII. The active phosphorylated form of TβRI recruits and phosphorylates downstream effector SMAD proteins, which can then translocate to the nucleus where they can regulate transcription. Non-canonical signaling by TGF-beta 1 can also be mediated through various pathways including MAPKs, small GTPases, and PI3Ks. TGF-beta proteins are synthesized as pro-proteins containing large amino-terminal pro-domains. These pro-domains allow proper folding and mediate the dimerization of TGF-beta monomers through a disulfide bridge. The pro-peptides are cleaved as TGF-beta is transported through the Golgi, however they remain associated in a noncovalent manner and help to regulate the activity and availability of mature TGF-beta. The TGF-beta pathway is a complex and finely tuned signaling network with a variety of biological functions. Depending on the cellular context TGF-beta can act as a tumor suppressor or an oncogene. For this reason mutation or misregulation of this pathway is seen in diverse cancer types from hematological malignancies to breast and prostate cancer (1).

In a recent study of developmental functions of TGF-beta 1, Wang et al. identified an important role in regulating follicular activation in the mouse ovary. They monitored the changing levels of endogenous protein during follicle development through western blotting with the TGF-beta 1 antibody (2). Covalently modified TGF-beta 1 antibodies have also proven useful in studies of development and disease. The Dimitroff group at Brigham and Women’s Hospital used PE-conjugated TGF-beta 1 antibodies for flow cytometry to analyze the modulation of adaptive immune responses (3). Biancotto et al. used biotinylated TGF-beta 1 antibodies to measure cytokine release by HIV infected lymph nodes using a multiplexed bead-based assay (4). These studies exemplify the versatility of modified TGF-beta 1 antibodies for a variety of applications and techniques.

Novus Biologicals offers TGF-beta 1 reagents for your research needs including:

PMIDs

  1. 22943793
  2. 24515103
  3. 20844192
  4. 17289812

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