Related Experiment Video
Updated: Aug 10, 2026
12:42
Photoactivated Localization Microscopy with Bimolecular Fluorescence Complementation (BiFC-PALM)
Published on: December 22, 2015
Disentangling information flow in the Ras-cAMP signaling network
Gregory W Carter1, Steffen Rupp, Gerald R Fink
1Institute for Systems Biology, Seattle, Washington 98103, USA. gcarter@systemsbiology.org
Genome Research
|March 15, 2006
Summary
Signal transduction involves complex, interconnected pathways influencing broad genomic expression changes, not isolated gene sets. This study maps these intricate signaling networks using a yeast model, revealing multiple information flow paths.
Area of Science:
- Molecular Biology
- Systems Biology
- Genomics
Background:
- Signal transduction pathways regulate gene expression.
- Genomic responses to signaling perturbations are complex and widespread.
- Existing models often simplify signal flow into isolated pathways.
Purpose of the Study:
- To investigate the complex, interconnected nature of signal transduction pathways.
- To model multiple, entangled information flow paths influencing gene expression.
- To develop testable hypotheses for genome-wide transcriptional responses.
Main Methods:
- Utilized the Ras-cAMP pathway in Saccharomyces cerevisiae as a model system.
- Perturbed key signaling elements and collected genome-wide expression data.
- Applied singular value decomposition to analyze transcriptional responses.
- Integrated molecular interaction data to link gene groups with signaling elements.
Main Results:
- Identified broad, varied, and complex changes in gene expression across the genome.
- Separated genome-wide transcriptional response into weighted expression components.
- Mapped multiple putative pathways of information flow through a dense signaling network.
- Connected specific gene groups to perturbed signaling elements.
Conclusions:
- Signal transduction is mediated by multiple, entangled pathways influencing overlapping gene sets.
- The developed network model provides insights into complex gene-expression regulation.
- This approach generates testable hypotheses for understanding signaling networks.
Related Concept Videos
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:25Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:22Amplifying Signals via Enzymatic Cascade
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 the...