SKAP55 Coupled with CD45 Positively Regulates T-Cell Receptor-Mediated Gene Transcription

Wu, Liangtang; Fu, Jun; Shen, Shi-Hsiang

doi:10.1128/mcb.22.8.2673-2686.2002

Cited by 37 publications

(32 citation statements)

References 34 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We occasionally observed a decrease in SKAP-55 Ϫ/Ϫ thymic cellularity; however, when averaged over six animals, this difference was not found to be statistically significant. This differs from the observations for ADAP Ϫ/Ϫ mice, which showed a moderate decrease in thymocyte numbers (10,27,43). In instances of mice with decreased numbers of thymocytes, the cells showed an increased propensity to undergo cell death in media (data not shown).…”

Section: Discussioncontrasting

confidence: 54%

“…SKAP-55 binds with high stoichiometry to ADAP (4,25), an interaction that is mediated by binding of the SKAP-55 SH3 domain to a proline-rich region in ADAP (23,25) and by weaker binding of the ADAP SH3c domain to a tyrosine-based RKXXYXXY motif in SKAP-55 (7,14). SKAP-55 may also interact with the D1 domain of the phosphatase CD45 (43). We have previously shown that SKAP-55 is capable of enhancing TCR-mediated activation of ␤1 and ␤2 integrins and of forming conjugates between T cells and APCs (40) and that small interfering RNA-mediated knockdown of SKAP-55 impairs conjugate formation and LFA-1 clustering in mouse T cells (13).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Wang

Liu

et al. 2007

Molecular and Cellular Biology

View full text Add to dashboard Cite

T-cell receptors (TCRs) undergo microclustering and supramolecular activation cluster formation at the immunological synapse (IS) during conjugation between T cells and antigen-presenting cells (APCs) (5,21,35). Microclustering can in turn activate GTP-binding proteins, protein kinases, phosphatases, and the phosphorylation of adaptor proteins. CD4-and CD8-p56lck activation leads to immunoreceptor tyrosinebased activation motif phosphorylation on the CD3 and TCR chains, the recruitment of ZAP-70 (zeta-associated proteintyrosine kinase of 70 kDa), and the activation of TEC kinases ITK/RLK (interleukin-2-inducible/resting lymphocyte kinase) (1,(31)(32)(33)41). Adaptor proteins possess binding sites and domains needed for complex-complex formation (31,32,41). Immune cell-specific adaptors include LAT (linker for activation of T cells), GADS (Grb-2-like adaptor downstream of Shc), SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa), ADAP (adhesion-and degranulation-promoting adaptor protein; previously known as FYN T-binding protein/SLP-76-associated protein [FYB/SLAP]), and SKAP-55 (Src kinase-associated phosphoprotein of 55 kDa; also known as SCAP1) (3,23,24,26,31,32,(40)(41)(42). Phosphorylation of LAT recruits phospholipase C␥1, Grb-2, and GADS-SLP-76 and induces Ca 2ϩ mobilization and cytokine transcription (32,33,41,44).Binding of leukocyte function-associated antigen 1 (LFA-1; also known as CD11/CD18 or ␣ L ␤ 2 ) to intercellular adhesion molecules 1 and 2 (ICAM-1 and -2) on APCs mediates T-cell-APC conjugation (5,8,11,21,37). Following initial adhesion, TCR/CD3 ligation induces signals (i.e., "inside-out signaling") that further activate integrin adhesion (2,5,8,11,37). Conversion of LFA-1 to intermediate-or higher-affinity forms involves changes in conformation and receptor clustering (11,37). Multiple signaling proteins mediate this process. They include the GTP-binding protein Rap-1, its ligand RapL (regulator of cell adhesion and polarization enriched in lymphoid tissues), RIAM (Rap1-GTP-interacting adaptor molecule), the guanine nucleotide exchange factor Vav-1, and the adaptors ADAP,10,13,15,16,17,18,20,22,27,28,34). The protein-tyrosine kinase ZAP-70 phosphorylates YESP sites in SLP-76, which allows binding to the Src homology 2 (SH2) domain of Vav-1 (29), while the SH2 domain of SLP-76 binds to two YDDV sites in ADAP (30, 39). T-cell lines lacking SLP-76 show impaired superantigen-induced conjugation (44). ADAP is an immune cell-specific adaptor with a unique N-terminal region, a proline-rich region, a canonical and a noncanonical SH3 domain, one Ena/VASP homology 1 (EVH1) binding domain, and two putative nuclear localization motifs (3,4,19,26,31). ADAP is preferentially phosphorylated by the Src kinase p59fynT (4,25) and can cooperate with p59 fynT and SLP-76 in amplifying TCR-induced interleukin-2 (IL-2) transcription (30). The adaptor can up-regulate integrin-mediated adhesion in certain basophilic cell lines (9), while ADAP Ϫ/Ϫ T cells show profound defects in ␤1 and ␤2 integrin clusterin...

show abstract

Section: Discussioncontrasting

confidence: 54%

mentioning

confidence: 99%

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

Wang

Liu

et al. 2007

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…In contrast, CD45 has no known ligand on the APC to hold it at the synapse, and the large lumenal domain of CD45 may simply be restricted from diffusing into the tight ring of adhesion mediated by LFA-1/ICAM interactions. Alternatively, LFA-1-mediated actin polymerization may generate a cytoskeletal fence that restricts the diffusion of CD45 into the immunological synapse because of it large cytosolic phosphatase domain or indirectly through the interaction of the cytosolic tail of CD45 with fodrin (75) or with SKAP55 (76).…”

Section: Discussionmentioning

confidence: 99%

LFA-1-Mediated T Cell Costimulation through Increased Localization of TCR/Class II Complexes to the Central Supramolecular Activation Cluster and Exclusion of CD45 from the Immunological Synapse

Graf¹,

Bushnell

Miller

2007

The Journal of Immunology

View full text Add to dashboard Cite

T cell activation is associated with a dramatic reorganization of cell surface proteins and associated signaling components into discrete subdomains within the immunological synapse in T cell:APC conjugates. However, the signals that direct the localization of these proteins and the functional significance of this organization have not been established. In this study, we have used wild-type and LFA-1-deficient, DO11.10 TCR transgenic T cells to examine the role of LFA-1 in the formation of the immunological synapse. We found that coengagement of LFA-1 is not required for the formation of the central supramolecular activation cluster (cSMAC) region, but does increase the accumulation of TCR/class II complexes within the cSMAC. In addition, LFA-1 is required for the recruitment and localization of talin into the peripheral supramolecular activation cluster region and exclusion of CD45 from the synapse. The ability of LFA-1 to increase the amount of TCR engaged during synapse formation and segregate the phosphatase, CD45, from the synapse suggests that LFA-1 might enhance proximal TCR signaling. To test this, we combined flow cytometry-based cell adhesion and calcium-signaling assays and found that coengagement of LFA-1 significantly increased the magnitude of the intracellular calcium response following Ag presentation. These data support the idea that in addition to its important role on regulating T cell:APC adhesion, coengagement of LFA-1 can enhance T cell signaling, and suggest that this may be accomplished in part through the organization of proteins within the immunological synapse.

show abstract

“…The samples were centrifuged at 14,000 rpm (20,000 ϫ g) for 10 min at 4°C. An aliquot of this whole cell lysate was removed, and the remaining lysate was subjected to immunoprecipitation as described previously (40). The proteins were resolved on a 7.5% SDS-PAGE gel and transferred to nitrocellulose membranes (Hybond-ECL).…”

mentioning

confidence: 99%

PTEN Associates with the Vault Particles in HeLa Cells

Fotouhi‐Ardakani

et al. 2002

Journal of Biological Chemistry

Self Cite

104

View full text Add to dashboard Cite

PTEN is a tumor suppressor that primarily dephosphorylates phosphatidylinositol 3,4,5-trisphosphate to down-regulate the phosphoinositide 3-kinase/Akt signaling pathway. Although the cellular functions of PTEN as a tumor suppressor have been well characterized, the mechanism by which PTEN activity is modulated by other signal molecules in vivo remains poorly understood. In searching for potential PTEN modulators through protein-protein interaction, we identified the major vault protein (MVP) as a dominant PTENbinding protein in a yeast two-hybrid screen. MVP is the major structural component of vault, the largest intracellular ribonucleoprotein particle. PTEN was originally identified as a tumor suppressor gene based on its high frequency of mutation in a variety of tumors (1-3). Germ-line mutations of PTEN are the cause of Cowden disease, an autosomal-dominant hamartoma syndrome that results in an increased risk for development of tumors in a variety of tissues (4 -7). The genetic evidence that PTEN is an important tumor suppressor is supported by the fact that heterozygous disruption of the PTEN gene in knockout mice results in the spontaneous development of tumors (8 -10). Although PTEN as a protein phosphatase is capable of dephosphorylating tyrosine and threonine/serine residues (11, 12), the primary substrates of PTEN are 3Ј-phosphoinositides, PtdIns-3,4-P 2 and PtdIns-3,4,5-P 3 (13). Genetic and biochemical studies have demonstrated that the tumor suppressor functions of PTEN are linked primarily with the lipid phosphatase activity and its association with the well defined phosphoinositide 3-kinase pathway (reviewed in Refs. 14 -20). Substantial progress has been made in the characterization of PTEN as a tumor suppressor as well as in the regulation of many cellular processes including growth, adhesion, migration, invasion, and apoptosis. Nevertheless, the mechanism by which PTEN activity is modulated in various cellular signaling complexes remains elusive. It is assumed that the activity and the cellular function of PTEN may be regulated through in vivo proteinprotein interactions. PTEN contains a number of putative regulatory modules, including the N-terminal phosphoinositide binding motif, a C2 domain, a PDZ-binding site, and two proline-, glutamic acid-, serine-, and threonine-rich segments (21). The C2 domain of PTEN has been implicated in mediating membrane association (22). The C-terminal tail of PTEN interacts with several PDZ domain-containing proteins such as hDLG, hMAST205, MAGI-2, and MAGI-3 (23-25). The interaction of PTEN with these proteins may be important for its biological function, as it has been reported that MAGI-2 and MAGI-3 can enhance the activity of PTEN (23, 24). In contrast, several groups found that the PDZ-binding site of PTEN is not required for tumor suppression or other biological activities (21,(25)(26)(27)(28). Therefore, the complete spectrum of PTEN-interacting proteins and the effects of the interactions on PTEN function are not yet defined.To date, the vault complex w...

show abstract

SKAP55 Coupled with CD45 Positively Regulates T-Cell Receptor-Mediated Gene Transcription

Cited by 37 publications

References 34 publications

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

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

LFA-1-Mediated T Cell Costimulation through Increased Localization of TCR/Class II Complexes to the Central Supramolecular Activation Cluster and Exclusion of CD45 from the Immunological Synapse

PTEN Associates with the Vault Particles in HeLa Cells

Contact Info

Product

Resources

About