Priming of CD2-induced p62Dok tyrosine phosphorylation by CD3 in Jurkat T cells

Harriague, Julie; Debré, Patrice; Bismuth, Georges; Hubert, Pascale

doi:10.1002/1521-4141(200011)30:11<3319::aid-immu3319>3.0.co;2-1

Cited by 6 publications

(6 citation statements)

References 40 publications

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“…We were unable to detect p62 dok tyrosine phosphorylation following CD3 engagement in either ZAP70-or LAT-deficient cells, and, indeed, CD3 engagement inhibited CD2-mediated p62 dok association with Crk-L; this CD3-dependent regulation required ZAP70 kinase expression. It is important to note that, in our studies, ligation of CD3 occurred concurrently with that of CD2; other outcomes may result from stimulating one receptor in advance of the other (39). It will be interesting to determine whether, with additional experimentation and other systems analyzed, the induction of p62 dok phosphorylation remains a qualitative difference between CD2 and TcR-CD3 signaling.…”

Section: Discussionmentioning

confidence: 84%

T Cell Regulation of p62 (Dok1) Association with Crk-L

Martelli¹,

Boomer

et al. 2001

Journal of Biological Chemistry

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In addition to engagement of the T cell receptor-CD3 complex, T lymphocytes can be activated by a variety of cell surface molecules including the ϳ50-kDa surface receptor CD2. While the majority of biochemical signaling elements are triggered by either CD2 or TcR-CD3 receptors, a small number of proteins are engaged by only one receptor. Recently, p62 dok (Dok1), a member of the Dok family of adapter molecules, has been reported to be activated by CD2 and not by CD3 engagement. Here we have examined the role of p62 dok in CD2-dependent signaling in Jurkat T cells. As previously reported, we find that ligation of the CD2 molecule by mitogenic pairs of anti-CD2 mAbs led to phosphorylation of p62 dok . While CD2-induced p62 dok tyrosine phosphorylation was independent of both the p36/38 membrane adapter protein linker of activated T cells (LAT) and the ZAP70/Syk family of kinases, it was dependent upon the Src family of kinases including Lck and Fyn. We find further that CD2 engagement induced the association of tyrosine-phosphorylated p62 dok to Crk-L. The CD2-dependent association of p62 dok to Crk-L was independent of expression of the ZAP70/Syk family of kinases. Of note, while T cell receptor-CD3 engagement did not induce either p62 dok phosphorylation or Crk-L association in Jurkat T cells, it did inhibit CD2-dependent p62 dok -Crk-L complexes; this TcR-CD3-mediated regulation was dependent upon ZAP70 kinase activity. Our data suggest that phosphorylation of p62 dok and its interaction with other signaling proteins may depend upon integrated signals emanating from the CD2 receptor, utilizing a ZAP70/LAT-independent pathway, and the TcR-CD3 receptor, which is ZAP70/Syk-dependent. T cell antigen receptor (TCR)1 engagement by specific antigen embedded within MHC proteins or by anti-CD3 mAb triggers a complex network of biochemical signal transduction events that direct the functional program of the T cell (1). Early T cell biochemical signaling involves Src (Lck and Fyn)-related tyrosine kinase activity leading to ZAP70 kinase activity (2-5). Engagement of TcR-CD3 complexes leads to the recruitment of adaptor molecules and enzymes (protein tyrosine and serine/ threonine kinases and phosphatases) in a multicomponent signaling complex in specialized membrane domains termed lipid rafts (6, 7). Signal transduction culminates in transcriptional activation leading to cytokine production and cellular proliferation.The canonical early biochemical events that follow TcR-CD3 engagement may be mimicked by ligation, via mitogenic combinations of mAbs, of the CD2 molecule, a 50 -55-kDa glycoprotein expressed on the surface of essentially all human T and natural killer cells (8 -10). Pairs of anti-CD2 mAbs induce activation of the Src (Lck/Fyn) kinases, ZAP70 kinase, the adaptor molecules LAT and Cbl, and phosphatidylinositol 3-kinase, inter alia, leading to transcriptional activation of nuclear factor of activated T cells (NFAT) and cytokine (e.g. interleukin-2) production (11-20). Indeed, the remarkable similarity between t...

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Section: Discussionmentioning

confidence: 84%

T Cell Regulation of p62 (Dok1) Association with Crk-L

Martelli¹,

Boomer

et al. 2001

Journal of Biological Chemistry

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“…It may be added that, while CD2AP expression has been documented in mouse T cells, its expression pattern in human T cells is unclear, having only been demonstrated to be expressed in the T-cell leukemia cell line, Jurkat cells. 18,19,78,79 It is therefore possible that there are species-specific differences in the pattern of CD2AP expression. It may be added that Northern blotting studies have suggested that CD2AP is widely expressed in human tissues (with the exception of brain), 18,80 but Dustin et al (1998) reported a more restricted range of protein expression (assessed by Western blotting).…”

Section: Discussionmentioning

confidence: 99%

Novel markers of normal and neoplastic human plasmacytoid dendritic cells

Marafioti

Paterson

Ballabio

et al. 2008

Blood

202

169

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“…After centrifugation (5 min at 500 ϫ g), the supernatants were recovered and centrifuged at 40,000 ϫ g for 30 min at 4°C. The pellets were resuspended in buffer A and centrifuged at 40 …”

Section: Membrane Preparation and [ 35 S]gtp␥s Binding Assaymentioning

confidence: 99%

“…The percentage of phospho-Erk-1/2-positive cells was evaluated by flow cytometry. The same primary Ab was used in immunoblot experiments, using a reported protocol (40).…”

Section: Evaluation Of Cxcr4 Functionsmentioning

confidence: 99%

CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes

Balabanian

Harriague

Décrion

et al. 2004

The Journal of Immunology

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Interaction of HIV-1 envelope glycoprotein gp120 with the chemokine receptor CXCR4 triggers not only viral entry but also an array of signal transduction cascades. Whether gp120 induces an incomplete or aberrant set of signals, or whether it can function as a full CXCR4 agonist, remains unclear. We report that, in unstimulated human primary CD4+ T cells, the spectrum of signaling responses induced by gp120 through CXCR4 paralleled that induced by the natural ligand stromal cell-derived factor 1/CXCL12. gp120 activated heterotrimeric G proteins and the major G protein-dependent pathways, including calcium mobilization, phosphoinositide-3 kinase, and Erk-1/2 MAPK activation. Interestingly, gp120 caused rapid actin cytoskeleton rearrangements and profuse membrane ruffling, as evidenced by dynamic confocal imaging. This coordinated set of events resulted in a bona fide chemotactic response. Inactivated HIV-1 virions that harbored conformationally intact envelope glycoproteins also caused actin polymerization and chemotaxis, while similar virions devoid of envelope glycoproteins did not. Thus gp120, in monomeric as well as oligomeric, virion-associated form, elicited a complex cellular response that mimicked the effects of a chemokine. HIV-1 has therefore the capacity to dysregulate the vast CD4+ T cell population that expresses CXCR4. In addition, HIV-1 may exploit its chemotactic properties to retain potential target cells and locally perturb their cytoskeleton, thereby facilitating viral transmission.

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Priming of CD2-induced p62Dok tyrosine phosphorylation by CD3 in Jurkat T cells

Cited by 6 publications

References 40 publications

T Cell Regulation of p62 (Dok1) Association with Crk-L

T Cell Regulation of p62 (Dok1) Association with Crk-L

Novel markers of normal and neoplastic human plasmacytoid dendritic cells

CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes

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