TGF beta receptor 2

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Overview

Structure of TGF beta receptor 2

The TGF beta receptor 2 (TGFBR2) is a transmembrane serine/threonine kinase that plays a critical role in the transforming growth factor beta (TGF-_) signaling pathway. This receptor is involved in a wide range of cellular processes, including cell growth, cell differentiation, apoptosis, and cellular homeostasis.

Structure

TGF beta receptor 2 is composed of an extracellular domain, a transmembrane domain, and an intracellular kinase domain. The extracellular domain is responsible for binding the TGF-_ ligand, while the intracellular domain transduces the signal through phosphorylation of downstream signaling molecules.

Function

TGF beta receptor 2 functions as part of a receptor complex. Upon binding of TGF-_, TGFBR2 forms a heteromeric complex with TGF beta receptor 1 (TGFBR1). This complex phosphorylates and activates SMAD proteins, which then translocate to the nucleus to regulate the expression of target genes.

Signaling Pathway

The TGF-_ signaling pathway is initiated when TGF-_ ligands bind to TGFBR2. This binding induces the recruitment and phosphorylation of TGFBR1. Activated TGFBR1 phosphorylates receptor-regulated SMADs (R-SMADs), such as SMAD2 and SMAD3. These R-SMADs form a complex with SMAD4 and translocate to the nucleus to modulate gene expression.

Clinical Significance

Mutations in the TGFBR2 gene have been associated with various diseases, including Marfan syndrome, Loeys-Dietz syndrome, and certain types of cancer. The receptor's role in regulating cell proliferation and apoptosis makes it a critical factor in tumor suppression and progression.

Research and Therapeutic Implications

Understanding the function and regulation of TGF beta receptor 2 is crucial for developing therapeutic strategies for diseases associated with its dysfunction. Targeting the TGF-_ signaling pathway holds potential for treating fibrotic diseases, cancer, and other conditions involving aberrant cell signaling.

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Contributors: Prab R. Tumpati, MD