TGFβ/SMAD signaling pathway
The TGFβ/SMAD signaling pathway is a criticalsignaling transduction route that plays a key role in various cellular processes such as cell proliferation, differentiation, migration, and apoptosis.
TGFβ Superfamily Ligands: TGFβ (Transforming Growth Factor-beta) is a multifunctional cytokine that belongs to the TGFβ superfamily, which includes a variety of ligands such as TGFβ1, TGFβ2, TGFβ3, etc.
Receptor Binding: TGFβ binds to the serine/threonine kinase receptors on the cell surface, which typically consist of two transmembrane proteins known as Type I and Type II receptors.
Receptor Activation: After binding to TGFβ, the Type II receptor phosphorylates and activates the Type I receptor, leading to a conformational change in the receptor complex.
Activation of SMAD Proteins: The activation of the Type I receptor further leads to the phosphorylation of the Receptor-Regulated SMADs (R-SMADs) within the SMAD protein family, including SMAD2 and SMAD3.
SMAD Complex Formation: The phosphorylated R-SMADs bind to the Common Partner SMAD (Co-SMAD), which is SMAD4, forming a SMAD complex.
Nuclear Translocation: The SMAD complex enters the cell nucleus through the nuclear pore and interacts with specific binding sites on DNA, regulating the transcription of target genes.
Regulation of Target Genes: The SMAD complex can act as a transcriptional activator or repressor, controlling the expression of various target genes involved in cell cycle control, cell differentiation, extracellular matrix synthesis, and other biological processes.
Signal Termination: The duration of SMAD signaling is regulated by phosphatases, such as PPM1A and the SMURF family proteins, which can remove the phosphorylation from SMAD proteins, terminating the signal transduction.
Disease Association: Abnormal regulation of the TGFβ/SMAD signaling pathway is associated with various diseases, including fibrotic diseases, certain cancers, and developmental abnormalities.
Therapeutic Potential: Due to the role of the TGFβ/SMAD signaling pathway in disease development, it has become an important target for drug development, especially in the fields of cancer and fibrosis therapy.
Drug Targets
