ArticleThe Journal of biological chemistry2006
Antagonism or synergism. Role of tyrosine phosphatases SHP-1 and SHP-2 in growth factor signaling.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Hypoxia Impairs NK Cell Cytotoxicity through SHP-1-Mediated Attenuation of STAT3 and ERK Signaling Pathways.Journal of immunology research · 2020Article
- Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks.PloS one · 2017Article
- PTPN6 expression is epigenetically regulated and influences survival and response to chemotherapy in high-grade gliomas.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Abrogation of SRC homology region 2 domain-containing phosphatase 1 in tumor-specific T cells improves efficacy of adoptive immunotherapy by enhancing the effector function and accumulation of short-lived effector T cells in vivo.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Reactive oxygen species and epidermal growth factor are antagonistic cues controlling SHP-2 dimerization.Molecular and cellular biology · 2012Article
- Role of STAT3 in Transformation and Drug Resistance in CML.Frontiers in oncology · 2012Article
- Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.Experimental diabetes research · 2012Article
- Cyclic GMP and protein kinase G control a Src-containing mechanosome in osteoblasts.Science signaling · 2010Article
- Prolactin enhances insulin-like growth factor I receptor phosphorylation by decreasing its association with the tyrosine phosphatase SHP-2 in MCF-7 breast cancer cells.The Journal of biological chemistry · 2010Article
- SHP-2 expression negatively regulates NK cell function.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Global liver proteomics of rats exposed for 5 days to phenobarbital identifies changes associated with cancer and with CYP metabolism.Toxicological sciences : an official journal of the Society of Toxicology · 2008Article
- Suppression of proximal T cell receptor signaling and lytic function in CD8+ tumor-infiltrating T cells.Cancer research · 2007Article
- The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.Histology and histopathology · 2007Review
- LPS-induced down-regulation of signal regulatory protein {alpha} contributes to innate immune activation in macrophages.The Journal of experimental medicine · 2007Article
- Arsenite and insulin exhibit opposing effects on epidermal growth factor receptor and keratinocyte proliferative potential.Toxicology and applied pharmacology · 2007Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
SHP-1 and SHP-2 are two Src homology 2 domain-containing tyrosine phosphatases with major pathological implications in cell growth regulating signaling. They share significant overall sequence identity, but their biological functions are often opposite. SHP-1 is generally considered as a negative signal transducer and SHP-2 as a positive one. However, the precise role of each enzyme in shared signaling pathways is not well defined. In this study, we investigated the interaction of these two enzymes in a single cell system by knocking down their expressions with small interfering RNAs and analyzing the effects on epidermal growth factor signaling. Interestingly, knockdown of either SHP-1 or SHP-2 caused significant reduction in the activation of ERK1/2 but not Akt. Furthermore, SHP-1, SHP-2, and Gab1 formed a signaling complex, and SHP-1 and SHP-2 interact with each other. The interaction of SHP-1 with Gab1 is mediated by SHP-2 because it was abrogated by knockdown of SHP-2, and SHP-2, but not SHP-1, binds directly to tyrosine-phosphorylated Gab1. Together, the data revealed that both SHP-1 and SHP-2 have a positive role in epidermal growth factor-induced ERK1/2 activation and that they act cooperatively rather than antagonistically. The interaction of SHP-1 and SHP-2 may be responsible for previously unexpected novel regulatory mechanism of cell signaling by tyrosine phosphatases.
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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.