Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor<sup>1</sup>

Wenzel, Jennifer M.; Sanzenbacher, Ralf; Ghadimi, Markus Philipp; Lewitzky, Marc; Zhou, Qingchun; Kaplan, David R.; Kabelitz, Dieter; Feller, Stephan M.; Janßen, Ottmar

doi:10.1016/s0014-5793(01)03174-x

Cited by 52 publications

(55 citation statements)

References 57 publications

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“…These include the Src-like kinases Fyn, Lyn, and Fgr and the adaptor proteins Nck, Grb2 and PSTPIP. 28,[35][36][37][38][39] Of interest is the recently described interaction between Nck and FasL, as Nck likely links preformed and granule-stored FasL to WASP and the cytoskeleton. 38 In agreement with our observation that PMA-induced FasL degranulation was latrunculin B-sensitive it was found that the delivery of FasL to the immunological synapse was dependent on actin filament formation.…”

Section: Discussionmentioning

confidence: 99%

Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells

et al. 2008

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Fas (CD95/Apo-1) ligand is a potent inducer of apoptosis and one of the major killing effector mechanisms of cytotoxic T cells. Thus, Fas ligand activity has to be tightly regulated, involving various transcriptional and post-transcriptional processes. For example, preformed Fas ligand is stored in secretory lysosomes of activated T cells, and rapidly released by degranulation upon reactivation. In this study, we analyzed the minimal requirements for activation-induced degranulation of Fas ligand. T cell receptor activation can be mimicked by calcium ionophore and phorbol ester. Unexpectedly, we found that stimulation with phorbol ester alone is sufficient to trigger Fas ligand release, whereas calcium ionophore is neither sufficient nor necessary. The relevance of this process was confirmed in primary CD4 þ and CD8 þ T cells and NK cells. Although the activation of protein kinase(s) was absolutely required for Fas ligand degranulation, protein kinase C or A were not involved. Previous reports have shown that preformed Fas ligand co-localizes with other markers of cytolytic granules. We found, however, that the activationinduced degranulation of Fas ligand has distinct requirements and involves different mechanisms than those of the granule markers CD63 and CD107a/Lamp-1. We conclude that activation-induced degranulation of Fas ligand in cytotoxic lymphocytes is differently regulated than other classical cytotoxic granule proteins.

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Section: Discussionmentioning

confidence: 99%

Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells

et al. 2008

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“…10 After centrifugation, cell lysates were incubated for at least 90 min. rotating at 4 C with the respective GST fusion protein (20-40 lg) and glutathione sepharose beads (GE Healthcare).…”

Section: (Co)-immunoprecipitationmentioning

confidence: 99%

The adapter protein Nck: Role of individual SH3 and SH2 binding modules for protein interactions in T lymphocytes

et al. 2010

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Nck is a ubiquitously expressed, primarily cytosolic adapter protein consisting of one SH2 domain and three SH3 domains. It links receptor and nonreceptor tyrosine kinases to actin cytoskeleton reorganizing proteins. In T lymphocytes, Nck is a crucial component of signaling pathways for T cell activation and effector function. It recruits actin remodeling proteins to T cell receptor (TCR)-associated activation clusters and thereby initiates changes in cell polarity and morphology. Moreover, Nck is crucial for the TCR-induced mobilization of secretory vesicles to the cytotoxic immunological synapse. To identify the interactome of Nck in human T cells, we performed a systematic screen for interaction partners in untreated or pervanadate-treated cells. We used GST fusion proteins containing full length Nck, the combined SH3 domains or the individual SH3 and SH2 domains to precipitate putative Nck interactors from cellular lysates. Protein bands were excised from gels, processed by tryptic in-gel digestion and analyzed by mass spectrometry. Using this approach, we confirmed previously established interactions (e.g., with Slp76, CD3e, WASP, and WIPF1) and identified several novel putative Nck-binding proteins. We subsequently verified the SH2 domain binding to the actin-binding protein HIP55 and to FYB/ADAP, and the SH3-mediated binding to the nuclear proteins SFPQ/NONO. Using laser scanning microscopy, we provide new evidence for a nuclear localization of Nck in human T cells. Our data highlight the fundamental role of Nck in the TCR-to-cytoskeleton crosstalk and point to yet unknown nuclear functions of Nck also in T lymphocytes.

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“…In general, ligand/receptor interactions of members of these families regulate key events in cellular activation, proliferation, differentiation, cell death and survival of immune cells and other tissues. 53 Since most of the TNF family members act as membrane-bound factors and 54 ). Thus, the ligand/ receptor complexes of OX40L/CD134 (TNFSF4/TNFRSF4), CD154/CD40 (TNFSF5/TNFRSF5), CD70/CD27 (TNFSF7/ TNFRSF7), CD153/CD30 (TNFSF8/TNFRSF8), 4-1BB-L/ CD137 (TNFSF9/TNFRSF9), TRANCE/RANK (TNFSF11/ TNFRSF11), LIGHT/LIGHTR (TNFSF14/TNFRSF14) [55][56][57] and the death factors TNF, TRAIL (TNFSF10) 58 and CD95L (TNFSF6) were reported to convey retrograde signals.…”

Section: Cd95l and Other Bidirectional Signal Transducers With Cki Sumentioning

confidence: 99%

CD95 ligand - death factor and costimulatory molecule?

et al. 2003

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The CD95 ligand is involved as a death factor in the regulation of activation-induced cell death, establishment of immune privilege and tumor cell survival. In addition, CD95L may serve as a costimulatory molecule for T-cell activation. Alterations in expression or shedding of membrane and soluble CD95L are associated with numerous diseases, and underscore the pathophysiological relevance of the CD95/CD95L system. In most cases, the causal link between altered CD95L expression and pathophysiology is unknown. Given the potency of the molecule to regulate death and survival of many different cell types, the control of CD95L production, transport, storage, shedding and inactivation is of tremendous biological and clinical interest. This review summarizes the current knowledge, hypotheses and controversies about CD95L as a multifunctional ligand and receptor. It considers the different roles of membrane and soluble forms of CD95L and the complex networks of intracellular dynamics of protein trafficking, as well as the potential bidirectional signal transduction capacity of CD95L, with a focus on molecular interactions that have been worked out over the past years.

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Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor¹

Cited by 52 publications

References 57 publications

Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells

Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells

The adapter protein Nck: Role of individual SH3 and SH2 binding modules for protein interactions in T lymphocytes

CD95 ligand - death factor and costimulatory molecule?

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Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor1

Cited by 52 publications

References 57 publications

Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells

Distinct requirements for activation-induced cell surface expression of preformed Fas/CD95 ligand and cytolytic granule markers in T cells

The adapter protein Nck: Role of individual SH3 and SH2 binding modules for protein interactions in T lymphocytes

CD95 ligand - death factor and costimulatory molecule?

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Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor¹