An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R

Lymphocyte function-associated antigen (LFA)-1 clustering, which is needed for high avidity binding to intercellular adhesion molecule (ICAM)-1 and -2, regulates T cell motility and T cell–antigen-presenting cell (APC) conjugation. In this study, down-regulation of SKAP-55 by small interfering RNAs (siRNAs) identified an essential role for this adaptor molecule in the T cell receptor (TCR)–mediated ”inside-out signaling” that is needed for LFA-1 clustering and T cell–APC conjugation. In contrast, down-regulation of SKAP-55 had no effect on TCR–CD3 clustering. Furthermore, the expression of the related protein SKAP-55R failed to compensate for the loss of SKAP-55 in LFA-1 clustering, indicating that SKAP-55 has a unique function that cannot be replaced by this closely related protein. Our findings therefore indicate that SKAP-55, unlike SKAP-55R, is specifically tailored as an essential component of the inside-out signaling events that couple the TCR to LFA-1 clustering and T cell–APC conjugation.

• Publication year

  2005

• Venue

  Journal of Experimental Medicine

• Publication date

  2005-06-06

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/jem.20042577PMID 15939789PMCID 2213273
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• What is the importance of the immunological synapse?

  2004cited by this paper
• T cell killing does not require the formation of a stable mature immunological synapse

  2004cited by this paper
• ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation

  2004cited by this paper
• Imaging immune cell interactions and functions: SMACs and the Immunological Synapse.

  2003cited by this paper
• RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1

  2003cited by this paper
• T-cell integrins: more than just sticking points

  2003cited by this paper
• SKAP-55 regulates integrin adhesion and formation of T cell–APC conjugates

  2003cited by this paper
• The Size of the Synaptic Cleft and Distinct Distributions of Filamentous Actin, Ezrin, CD43, and CD45 at Activating and Inhibitory Human NK Cell Immune Synapses 12

  2003cited by this paper
• The Immunological Synapse Balances T Cell Receptor Signaling and Degradation

  2003cited by this paper
• Spread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton

  2003cited by this paper
• Staging and resetting T cell activation in SMACs

  2002cited by this paper
• Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling

  2002cited by this paper
• T Cell Receptor Signaling Precedes Immunological Synapse Formation

  2002cited by this paper
• SKAP55 Coupled with CD45 Positively Regulates T-Cell Receptor-Mediated Gene Transcription

  2002cited by this paper
• Sustained and dynamic inositol lipid metabolism inside and outside the immunological synapse

  2002cited by this paper
• Integrin activation and structural rearrangement

  2002cited by this paper
• Rap1 Functions as a Key Regulator of T-Cell and Antigen-Presenting Cell Interactions and Modulates T-Cell Responses

  2002cited by this paper
• Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells.

  2002cited by this paper
• The immunological synapse.

  2001cited by this paper
• Adaptor FYB (Fyn-binding protein) regulates integrin-mediated adhesion and mediator release: Differential involvement of the FYB SH3 domain

  2001cited by this paper
• Positive Regulation of T Cell Activation and Integrin Adhesion by the Adapter Fyb/Slap

  2001cited by this paper
• Coupling of the TCR to Integrin Activation by SLAP-130/Fyb

  2001cited by this paper
• SH3 domain recognition of a proline‐independent tyrosine‐based RKxxYxxY motif in immune cell adaptor SKAP55

  2000cited by this paper
• Adaptors and molecular scaffolds in immune cell signaling.

  1999cited by this paper
• Adaptors and Molecular Scaffolds in Immune Cell Signaling

  1999cited by this paper
• Molecular Interaction between the Fyn-associated Protein SKAP55 and the SLP-76-associated Phosphoprotein SLAP-130*

  1998cited by this paper
• FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells.

  1998cited by this paper
• SKAP‐HOM, a novel adaptor protein homologous to the FYN‐associated protein SKAP55 1

  1998cited by this paper
• Molecular Cloning of SKAP55, a Novel Protein That Associates with the Protein Tyrosine Kinase p59 fyn in Human T-lymphocytes*

  1997cited by this paper
• Induction of T cell adhesion by antigen stimulation and modulation by the coreceptor CD4.

  1996cited by this paper

• SKAP2 acts downstream of CD11b/CD18 and regulates neutrophil effector function

  2024cites this paper
• Multi-functional adaptor SKAP1: regulator of integrin activation, the stop-signal, and the proliferation of T cells

  2023cites this paper
• SKAP2—A Molecule at the Crossroads for Integrin Signalling and Immune Cell Migration and Function

  2023cites this paper
• The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events

  2021cites this paper
• PI3K in T Cell Adhesion and Trafficking

  2021cites this paper
• GTPase-activating protein Rasal1 associates with ZAP-70 of the TCR and negatively regulates T-cell tumor immunity

  2019cites this paper
• Immune adaptor SKAP1 acts a scaffold for Polo-like kinase 1 (PLK1) for the optimal cell cycling of T-cells

  2019cites this paper
• Skap2 Regulates Atherosclerosis through Macrophage Polarization and Efferocytosis

  2019cites this paper
• Immune adaptor protein SKAP1 (SKAP-55) forms homodimers as mediated by the N-terminal region

  2018cites this paper
• Phosphorylation of the α- and β-chains of LFA-1 regulates its interaction with cytoplasmic proteins and crosstalk to VLA-4 integrin

  2018cites this paper
• LRCH1 interferes with DOCK8-Cdc42–induced T cell migration and ameliorates experimental autoimmune encephalomyelitis

  2017cites this paper
• SKAP2 Promotes Podosome Formation to Facilitate Tumor-Associated Macrophage Infiltration and Metastatic Progression.

  2016cites this paper
• CD8+ Effector T Cell Migration to Pancreatic Islet Grafts Is Dependent on Cognate Antigen Presentation by Donor Graft Cells

  2016cites this paper
• Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1

  2016cites this paper
• T-cell immune adaptor SKAP1 regulates the induction of collagen-induced arthritis in mice

  2016cites this paper
• Memory T Cell Migration

  2015cites this paper
• ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy

  2015cites this paper
• Adaptor regulation of LFA‐1 signaling in T lymphocyte migration: Potential druggable targets for immunotherapies?

  2014cites this paper
• The N terminus of SKAP55 enables T cell adhesion to TCR and integrin ligands via distinct mechanisms

  2013influential citation
• Macrophages require Skap2 and Sirp&agr; for integrin-stimulated cytoskeletal rearrangement

  2012cites this paper
• CCR 7-mediated LFA-1 functions in T cells are regulated by 2 independent ADAP / SKAP 55 modules

  2012cites this paper
• Integrin signalling and function in immune cells

  2012cites this paper
• CCR7-mediated LFA-1 functions in T cells are regulated by 2 independent ADAP/SKAP55 modules.

  2012cites this paper
• Molekulare Eigenschaften des Integrin-regulierenden ADAP-SKAP55-Signalkomplexes

  2012cites this paper
• SKAP1 Protein PH Domain Determines RapL Membrane Localization and Rap1 Protein Complex Formation for T Cell Receptor (TCR) Activation of LFA-1

  2011cites this paper
• Autoimmune therapies targeting costimulation and emerging trends in multivalent therapeutics.

  2011cites this paper
• SKAP1 is dispensable for chemokine-induced migration of primary T-cells

  2010cites this paper
• Immunopathologies linked to integrin signalling

  2010cites this paper
• T cell receptor "inside-out" pathway via signaling module SKAP1-RapL regulates T cell motility and interactions in lymph nodes.

  2010cites this paper
• The role of Pyk2 and FAK in B cell migration, adhesion, and spreading

  2010cites this paper
• HPK1 Associates with SKAP-HOM to Negatively Regulate Rap1-Mediated B-Lymphocyte Adhesion

  2010cites this paper
• SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility

  2009cites this paper
• Phosphoinositide 3‐kinase‐regulated adapters in lymphocyte activation

  2009cites this paper
• β1 integrin regulation

  2009cites this paper
• Gene Related to Anergy in Lymphocytes (GRAIL) Expression in CD4+ T Cells Impairs Actin Cytoskeletal Organization during T Cell/Antigen-presenting Cell Interactions*

  2009cites this paper
• Adapters in the organization of mast cell signaling

  2009cites this paper
• The ins and outs of leukocyte integrin signaling.

  2009cites this paper
• SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1.

  2008cites this paper
• Distinct Regulation of Integrin-Dependent T Cell Conjugate Formation and NF-κB Activation by the Adapter Protein ADAP1

  2008cites this paper
• Adaptor SKAP-55 Binds p21ras Activating Exchange Factor RasGRP1 and Negatively Regulates the p21ras-ERK Pathway in T-Cells

  2008cites this paper
• LFA-1 Integrin beta2 Chain Phosphorylation Regulates Protein Interactions and Mediates Signals in T Cells

  2008cites this paper
• SKAP-55, SKAP-55-related and ADAP adaptors modulate integrin-mediated immune-cell adhesion.

  2008cites this paper
• Activation by the Adapter Protein ADAP B κ Cell Conjugate Formation and NF-Distinct Regulation of Integrin-Dependent T

  2008cites this paper
• Tec kinases, actin, and cell adhesion

  2007cites this paper
• Compartmentalization of ITAM and integrin signaling by adapter molecules

  2007cites this paper
• Functional Defects of SKAP-55-Deficient T Cells Identify a Regulatory Role for the Adaptor in LFA-1 Adhesion (cid:1)

  2007cites this paper
• Signal Transduction Events Regulating Integrin Function and T Cell Migration in the Mouse

  2007cites this paper
• T‐cell receptor signaling to integrins

  2007cites this paper
• Functional Defects of SKAP-55-Deficient T Cells Identify a Regulatory Role for the Adaptor in LFA-1 Adhesion

  2007cites this paper
• The molecular makeup and function of regulatory and effector synapses

  2007cites this paper
• RIAM Links the ADAP/SKAP-55 Signaling Module to Rap1, Facilitating T-Cell-Receptor-Mediated Integrin Activation

  2007influential citation
• In vivo disruption of T cell development by expression of a dominant‐negative polypeptide designed to abolish the SLP‐76/Gads interaction

  2007cites this paper
• Regulation of T‐cell antigen receptor‐mediated inside‐out signaling by cytosolic adapter proteins and Rap1 effector molecules

  2007influential citation
• Regulation and Function of SKAP-55 Non-canonical Motif Binding to the SH3c Domain of Adhesion and Degranulation-promoting Adaptor Protein*

  2006cites this paper
• Anatomy of the Lymphocyte function-associated antigen-1

  2006cites this paper
• CTLA-4 regulation of T cell function via RAP-1-mediated adhesion.

  2006cites this paper
• The ADAP/SKAP55 Signaling Module Regulates T-Cell Receptor-Mediated Integrin Activation through Plasma Membrane Targeting of Rap1

  2006cites this paper
• Regulation of In Vitro and In Vivo Immune Functions by the Cytosolic Adaptor Protein SKAP-HOM

  2005cites this paper
• T-cell signalling and immune system disorders

  2005cites this paper
• CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function.

  2005cites this paper