Related Experiment Video
Updated: Apr 13, 2026
11:38
Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
3.9K
Structural determinants of Smad function in TGF-β signaling.
Maria J Macias1, Pau Martin-Malpartida2, Joan Massagué3
1Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain.
Trends in Biochemical Sciences
|May 4, 2015
Summary
Smad transcription factors regulate transforming growth factor-β (TGF-β) signaling. Genetic variations in Smads influence their structure and function, impacting development and disease, with a new tool to explore these changes.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Smad transcription factors are key mediators of transforming growth factor-β (TGF-β) superfamily signaling.
- This signaling pathway is crucial for metazoan embryo development, tissue regeneration, and homeostasis.
- Conserved Smad proteins exhibit sequence variations across evolution, in human polymorphisms, and in cancer.
Purpose of the Study:
- To analyze the impact of genetic variations on Smad protein structure, regulation, and function.
- To provide a framework for understanding the significance of evolutionary and pathological sequence variations in Smads.
- To present a web application for comparative analysis of Smad sequences and structures.
Main Methods:
- Synthesis of existing mutational and structural data for Smad proteins.
- Bioinformatic analysis of Smad sequence variations.
- Structural visualization of Smad proteins and their disease-associated variants.
Main Results:
- Genetic variations in Smads can significantly alter their structure and function.
- Sequence variations are linked to evolutionary divergence, human polymorphisms, and cancer development.
- A web application was developed to facilitate the study of Smad variations.
Conclusions:
- Understanding Smad genetic variation is critical for comprehending developmental processes and disease pathogenesis.
- Structural and sequence analysis provides insights into Smad protein function and regulation.
- The developed web tool aids researchers in exploring Smad diversity and its implications.
Related Concept Videos
01:16TGF - β Signaling Pathway
11.0K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.0K
01:20The JAK-STAT Signaling Pathway
14.1K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
14.1K
02:33Hedgehog Signaling Pathway
10.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.4K
01:22Amplifying Signals via Enzymatic Cascade
19.6K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.6K
01:30Assembly of Signaling Complexes
7.2K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
7.2K
02:23Master Transcription Regulators
8.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K