ArticleThe FEBS journal2009
Toggle switches, pulses and oscillations are intrinsic properties of the Src activation/deactivation cycle.
Article in The FEBS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- Dynamic decoding of VEGF signaling and coordinated control of multiple phenotypes by the Src-TEM4-YAP pathway.Cell systems · 2025Article
- Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation.Journal of visualized experiments : JoVE · 2024Article
- Reengineering protein-phosphorylation switches.Science (New York, N.Y.) · 2021Article
- A systematic analysis of signaling reactivation and drug resistance.Cell reports · 2021Article
- Autophosphorylation and the Dynamics of the Activation of Lck.Bulletin of mathematical biology · 2021Article
- Light-regulated allosteric switch enables temporal and subcellular control of enzyme activity.eLife · 2020Article
- Spatial modeling of the membrane-cytosolic interface in protein kinase signal transduction.PLoS computational biology · 2018Article
- Repurposing cancer drugs to treat neurological diseases - Src inhibitors as examples.Neural regeneration research · 2017Article
- Src Family Kinases in Brain Edema After Acute Brain Injury.Acta neurochirurgica. Supplement · 2016Article
- Ubiquitin chain specific auto-ubiquitination triggers sustained oscillation, bistable switches and excitable firing.IET systems biology · 2014Article
- Phosphate sink containing two-component signaling systems as tunable threshold devices.PLoS computational biology · 2014Article
- Inhibition of SRC family kinases protects hippocampal neurons and improves cognitive function after traumatic brain injury.Journal of neurotrauma · 2014Article
- Article
- Guiding cell migration by tugging.Current opinion in cell biology · 2013Review
- Complexity of receptor tyrosine kinase signal processing.Cold Spring Harbor perspectives in biology · 2013Review
- When ubiquitination meets phosphorylation: a systems biology perspective of EGFR/MAPK signalling.Cell communication and signaling : CCS · 2013Review
- A computational model for early events in B cell antigen receptor signaling: analysis of the roles of Lyn and Fyn.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Article
- Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.PLoS computational biology · 2011Article
- B cell activation triggered by the formation of the small receptor cluster: a computational study.PLoS computational biology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Src-family kinases (SFKs) play a pivotal role in growth factor signaling, mitosis, cell motility and invasiveness. In their basal state, SFKs maintain a closed autoinhibited conformation, where the Src homology 2 domain interacts with an inhibitory phosphotyrosine in the C-terminus. Activation involves dephosphorylation of this inhibitory phosphotyrosine, followed by intermolecular autophosphorylation of a specific tyrosine residue in the activation loop. The spatiotemporal dynamics of SFK activation controls cell behavior, yet these dynamics remain largely uninvestigated. In the present study, we show that the basic properties of the Src activation/deactivation cycle can bring about complex signaling dynamics, including oscillations, toggle switches and excitable behavior. These intricate dynamics do not require imposed external feedback loops and occur at constant activities of Src inhibitors and activators, such as C-terminal Src kinase and receptor-type protein tyrosine phosphatases. We demonstrate that C-terminal Src kinase and receptor-type protein tyrosine phosphatase underexpression or their simultaneous overexpression can transform Src response patterns into oscillatory or bistable responses, respectively. Similarly, Src overexpression leads to dysregulation of Src activity, promoting sustained self-perpetuating oscillations. Distinct types of responses can allow SFKs to trigger different cell-fate decisions, where cellular outcomes are determined by the stimulation threshold and history. Our mathematical model helps to understand the puzzling experimental observations and suggests conditions where these different kinetic behaviors of SFKs can be tested experimentally.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.