Evaluating Function of Transmembrane Protein Tyrosine Phosphatase CD148 in Lymphocyte Biology

Harrod, Thomas; Justement, Louis B.

doi:10.1385/ir:26:1-3:153

Cited by 11 publications

(9 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a consequence, disruption of the expression of this molecule induces a spurious stimulation of T-lymphocytes that induce lymphadenopathy, splenomegaly, elevated levels of plasma IgGs, severe myocarditis, and pancreatitis (74). Other negative T-cell surface molecules include CD95, CD148, killer cell inhibitory receptors, PD1, and B-and T-lymphocyte attenuator (75)(76)(77)(78).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it has been shown that CTLA-4/CD152, PD1, and B-and T-lymphocyte attenuator contribute to the down-modulation of TCR signals by recruiting phosphatases such as SHP-2 and/or PP2A (74,75). CD148, a phosphatase itself, also binds to the intracellular signaling protein syntenin (78). We are currently performing both proteomic and two-hybrid experiments to identifying the proteins involved in the CD147 route.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CD147 Inhibits the Nuclear Factor of Activated T-cells by Impairing Vav1 and Rac1 Downstream Signaling

Ruíz¹,

Castro-Castro²,

Bustelo

2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

CD147 is a transmembrane protein that plays crucial roles in the development and function of the reproductive, visual, and nervous systems. CD147 also exerts positive and negative actions in T-cells by still obscure mechanisms. In this study, we have analyzed the expression, localization, and function of CD147 during T-cell receptor signaling responses. We show here that CD147 is an integral component of the T-cell immune synapse and that its overexpression leads to the inhibition of NF-AT (nuclear factor of activated T-cells) activity induced by Vav1, a Rac1 exchange factor. This inhibitory activity is mediated by the CD147 intracellular tail and is totally independent of its extracellular or transmembrane regions. The molecular dissection of the influence of CD147 on the Vav1 pathway indicates that its inhibitory action takes place downstream of Vav1 and Rac1 but upstream of the serine/threonine kinases JNK and Pak1. The interference of CD147 with these pathways is highly specific because the overexpression of CD147 does not affect the activity of other GDP/GTP exchange factors or the stimulation of the ERK cascade. Finally, we show that the CD147 knockdown in Jurkat cells promotes higher levels of NF-AT stimulation and Pak1 phosphorylation upon T-cell receptor cross-linking. Instead, the lack of CD147 does not affect other signaling cascades that participate in the same cellular response. Taken together, these results indicate that CD147, via the selective inhibition of specific downstream elements of the Vav1/Rac1 route, contributes to the negative regulation of T-cell responses.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CD147 Inhibits the Nuclear Factor of Activated T-cells by Impairing Vav1 and Rac1 Downstream Signaling

Ruíz¹,

Castro-Castro²,

Bustelo

2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…A focus on possible phosphorylation sites in the N-terminal has resulted in the discovery of a number of interactions and layers of regulation. Phosphorylation at tyrosine sites was shown to prevent interaction with receptor type protein tyrosine phosphates (rPTPnu) CD148 [28], and recent work pointed to an interesting interaction with ubiquitin (Ub), regulated by the N-terminal [29]. …”

Section: Mda-9/syntenin: Background On a Diverse Scaffolding Proteinmentioning

confidence: 99%

Targeting tumor invasion: the roles of MDA-9/Syntenin

Kegelman

Das

Emdad

et al. 2014

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

Introduction Melanoma differentiation-associated gene – 9 (MDA-9)/Syntenin has become an increasingly popular focus for investigation in numerous cancertypes. Originally implicated in melanoma metastasis, it has diverse cellular roles and is consistently identified as a regulator of tumor invasion and angiogenesis. As a potential target for inhibiting some of the most lethal aspects of cancer progression, further insight into the function of MDA-9/Syntenin is mandatory. Areas covered Recent literature and seminal articles were reviewed to summarize the latest collective understanding of MDA-9/Syntenin’s role in normal and cancerous settings. Insights into its participation in developmental processes are included, as is the functional significance of the N- and C-terminals and PDZ domains of MDA-9/Syntenin. Current reports highlight the clinical significance of MDA-9/Syntenin expression level in a variety of cancers, often correlating directly with reduced patient survival. Also presented are assessments of roles of MDA-9/Syntenin in cancer progression as well as its functions as an intracellular adapter molecule. Expert opinion Multiple studies demonstrate the importance of MDA-9/ Syntenin in tumor invasion and progression. Through the use of novel drug design approaches, this protein may provide a worthwhile therapeutic target. As many conventional therapies do not address, or even enhance, tumor invasion, an anti-invasive approach would be a worthwhile addition in cancer therapy.

show abstract

“…Direct evidence that the NTD and CTD regulate interactions between the PDZ domains of syntenin and target proteins is scarce but has been suggested by several studies. For example, tyrosine phosphorylation of the NTD has been reported to prevent the interaction of syntenin with the receptortype protein tyrosine phosphatase (rPTP) CD148, indicating that post-translational modifications of the NTD affect the interactions between the PDZ tandem and its targets (Harrod and Justement, 2002). Whether NTD phosphorylation affects the structure of the PDZ-domain tandem or oligomerization of syntenin, and thereby rPTP interactions, remains uncertain.…”

Section: A Role For the N-and C-terminal Domains Of Syntenin?mentioning

confidence: 99%

The ins and outs of syntenin, a multifunctional intracellular adaptor protein

Beekman

Coffer

2008

Journal of Cell Science

103

113

View full text Add to dashboard Cite

One of the most challenging issues currently facing cell biologists is how signal specificity and compartmentalization is achieved, allowing extracellular stimulation to result in a unique and predefined intracellular outcome. For this to occur, intracellular components must be correctly positioned in both space and time. Adaptor molecules, which contain protein-interaction domains, are often involved in the assembly of multimeric complexes that organize intracellular signal-transduction pathways. One such protein is syntenin, a PDZ-domain-containing molecule that has a surprising variety and diversity of interaction partners. Here we assimilate and discuss current data that support a role for syntenin in regulating transmembrane-receptor trafficking, tumour-cell metastasis and neuronal-synapse function.

show abstract

Evaluating Function of Transmembrane Protein Tyrosine Phosphatase CD148 in Lymphocyte Biology

Cited by 11 publications

References 27 publications

CD147 Inhibits the Nuclear Factor of Activated T-cells by Impairing Vav1 and Rac1 Downstream Signaling

CD147 Inhibits the Nuclear Factor of Activated T-cells by Impairing Vav1 and Rac1 Downstream Signaling

Targeting tumor invasion: the roles of MDA-9/Syntenin

The ins and outs of syntenin, a multifunctional intracellular adaptor protein

Contact Info

Product

Resources

About