ArticleCellular and molecular life sciences : CMLS2011
Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75).
Article in Cellular and molecular life sciences : CMLS, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 42 citations in OpenAlex.
- Computational Phosphosite-Specific Network Analysis of YES1 Y426 Reveals Cancer-Associated Phosphorylation Patterns.Proteomes · 2026Article
- The stress-activated kinase p38 mediates non-canonical activation of Src and tyrosine phosphorylation of the adapter protein TAB1.The Journal of biological chemistry · 2026Article
- Modulation of Functional Phosphorylation Sites by Basic Residues in the Unique Domain of c-Src.Molecules (Basel, Switzerland) · 2023Article
- Targeting the Src N-terminal regulatory element in cancer.Oncotarget · 2023Article
- Cross-Talk between Wnt Signaling and Src Tyrosine Kinase.Biomedicines · 2022Review
- Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis.Current biology : CB · 2022Article
- Article
- Regulatory Roles of the N-Terminal Intrinsically Disordered Region of Modular Src.International journal of molecular sciences · 2022Review
- Regulation, targets and functions of CHK.Frontiers in cell and developmental biology · 2022Review
- Quantitative phosphoproteomics uncovers dysregulated kinase networks in Alzheimer's disease.Nature aging · 2021Article
- Adhesion GPCR Latrophilin-2 Specifies Cardiac Lineage Commitment through CDK5, Src, and P38MAPK.Stem cell reports · 2021Article
- A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss of retinal ganglion cells in mice.Scientific reports · 2017Article
- Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development.Developmental biology · 2015Review
- The Cdk5 activator P39 specifically links muskelin to myosin II and regulates stress fiber formation and actin organization in lens.Experimental cell research · 2015Article
- Article
- The cyclin-dependent kinase family in the social amoebozoan Dictyostelium discoideum.Cellular and molecular life sciences : CMLS · 2014Review
- Cullin 5 destabilizes Cas to inhibit Src-dependent cell transformation.Journal of cell science · 2014Article
- Phosphorylation of unique domains of Src family kinases.Frontiers in genetics · 2014Review
- Rbx2 regulates neuronal migration through different cullin 5-RING ligase adaptors.Developmental cell · 2013Article
- Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase.Protein & cell · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75). Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation, is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75 or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75) is a physiologically significant mechanism of regulating intracellular Src activity.
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.