ArticleThe Journal of biological chemistry2014
Adaptor protein GRB2 promotes Src tyrosine kinase activation and podosomal organization by protein-tyrosine phosphatase ϵ in osteoclasts.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 32 citations in OpenAlex.
- PTPRE promotes gastric cancer cell resistance to 5-fluorouracil by inhibiting ferroptosis via the Src/FAK/TRIB3 axis.PloS one · 2026Article
- Exploring the PDZ, DUF, and LIM Domains of Pdlim5 in Dendrite Branching.International journal of molecular sciences · 2024Article
- The Configuration of GRB2 in Protein Interaction and Signal Transduction.Biomolecules · 2024Review
- Osteoclast Methods in Protein Phosphatase Research.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual.Genome biology · 2021Article
- Targeting M2 Macrophages Alleviates Airway Inflammation and Remodeling in Asthmatic MiceFrontiers in molecular biosciences · 2021Article
- PIP5k1β controls bone homeostasis through modulating both osteoclast and osteoblast differentiation.Journal of molecular cell biology · 2020Article
- ST5 Positively Regulates Osteoclastogenesis via Src/Syk/calcium Signaling Pathways.Molecules and cells · 2019Article
- Accelerated evolution and diversifying selection drove the adaptation of cetacean bone microstructure.BMC evolutionary biology · 2019Article
- Tuning the Protein Phosphorylation by Receptor Type Protein Tyrosine Phosphatase Epsilon (PTPRE) in Normal and Cancer Cells.Journal of Cancer · 2019Review
- Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor-Mediated T-Cell Function by an RNA-Based Mechanism.The Journal of infectious diseases · 2017Article
- Multifaceted Role of BTLA in the Control of CD8Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Article
- Pri-microRNA-124 rs531564 polymorphism minor allele increases the risk of pulmonary artery hypertension by abnormally enhancing proliferation of pulmonary artery smooth muscle cells.International journal of chronic obstructive pulmonary disease · 2017Article
- Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis.PloS one · 2017Article
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 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The non-receptor isoform of protein-tyrosine phosphatase ϵ (cyt-PTPe) supports adhesion of bone-resorbing osteoclasts by activating Src downstream of integrins. Loss of cyt-PTPe reduces Src activity in osteoclasts, reduces resorption of mineralized matrix both in vivo and in cell culture, and induces mild osteopetrosis in young female PTPe KO mice. Activation of Src by cyt-PTPe is dependent upon this phosphatase undergoing phosphorylation at its C-terminal Tyr-638 by partially active Src. To understand how cyt-PTPe activates Src, we screened 73 Src homology 2 (SH2) domains for binding to Tyr(P)-638 of cyt-PTPe. The SH2 domain of GRB2 bound Tyr(P)-638 of cyt-PTPe most prominently, whereas the Src SH2 domain did not bind at all, suggesting that GRB2 may link PTPe with downstream molecules. Further studies indicated that GRB2 is required for activation of Src by cyt-PTPe in osteoclast-like cells (OCLs) in culture. Overexpression of GRB2 in OCLs increased activating phosphorylation of Src at Tyr-416 and of cyt-PTPe at Tyr-638; opposite results were obtained when GRB2 expression was reduced by shRNA or by gene inactivation. Phosphorylation of cyt-PTPe at Tyr-683 and its association with GRB2 are integrin-driven processes in OCLs, and cyt-PTPe undergoes autodephosphorylation at Tyr-683, thus limiting Src activation by integrins. Reduced GRB2 expression also reduced the ability of bone marrow precursors to differentiate into OCLs and reduced the fraction of OCLs in which podosomal adhesion structures assume organization typical of active, resorbing cells. We conclude that GRB2 physically links cyt-PTPe with Src and enables cyt-PTPe to activate Src downstream of activated integrins in OCLs.
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.