Analysis of immunoreceptor tyrosine‐based activation motif (ITAM) binding to ZAP‐70 by surface plasmon resonance

Vély, Frederic; Nunès, Jacques A.; Malissen, Bernard; Hedgecock, Charles J. R.

doi:10.1002/eji.1830271138

Cited by 24 publications

(22 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The SH2-containing protein-tyrosine kinases ZAP-70 and Syk are the only effector molecules that associate in vivo with the phosphorylated form of ITAM-bearing molecules (33). The requirement of both tyrosines residues for complete KARAP/DAP-12 transducing function is consistent with the structure of ZAP-70 tandem SH2 domains, which dictates the simultaneous recruitment of both ITAM phosphotyrosines to a ZAP-70 SH2 tandem (34,35). The recently reported in vitro association between KARAP/DAP-12 phosphorylated peptides and ZAP-70/Syk is consistent with our in vivo point mutation analysis (26).…”

Section: Ubiquitous Expression Of Mouse Karap-itam-bearingmentioning

confidence: 61%

Gene Structure, Expression Pattern, and Biological Activity of Mouse Killer Cell Activating Receptor-associated Protein (KARAP)/DAP-12

Tomasello

Olcese

Vély

et al. 1998

Journal of Biological Chemistry

Self Cite

142

123

View full text Add to dashboard Cite

Natural killer cell and T cell subsets express at their cell surface a repertoire of receptors for MHC class I molecules, the natural killer cell receptors (NKRs). NKRs are characterized by the existence of inhibitory and activating isoforms, which are encoded by highly homologous but separate genes present in the same locus. Inhibitory isoforms express an intracytoplasmic immunoreceptor tyrosine-based inhibition motif, whereas activating isoforms lack any immunoreceptor tyrosinebased inhibition motif but harbor a charged amino acid residue in their transmembrane domain. We previously characterized KARAP (killer cell activating receptorassociated protein), a novel disulfide-linked tyrosinephosphorylated dimer that selectively associates with the activating NKR isoforms. We report here the identification of the mouse KARAP gene, its localization on chromosome 7 and its genomic organization in five exons. Point mutation and transfection studies revealed that KARAP is a novel signaling transmembrane subunit whose transduction function depends on the integrity of an intracytoplasmic immunoreceptor tyrosinebased activation motif. In contrast to previous members of the immunoreceptor tyrosine-based activation motif polypeptide family, KARAP is ubiquitously expressed on hematopoietic and nonhematopoietic cells, suggesting its association with a broad range of activating receptors in a variety of tissues.

show abstract

Section: Ubiquitous Expression Of Mouse Karap-itam-bearingmentioning

confidence: 61%

Gene Structure, Expression Pattern, and Biological Activity of Mouse Killer Cell Activating Receptor-associated Protein (KARAP)/DAP-12

Tomasello

Olcese

Vély

et al. 1998

Journal of Biological Chemistry

Self Cite

142

123

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…26,27 It has previously been shown that both Syk and ZAP-70 bind to Lck [28][29][30] and that in vitro, the 2 kinases bind to chain ITAMs with similar affinities. [31][32][33] Indeed, it has been hypothesized that ZAP-70 may promote ITAM phosphorylation by bringing Lck into the TCR-chain complex. 28,34 In view of these data, it has been perplexing that chain phosphorylation is compromised in ZAP-70-deficient thymocytes and T cells expressing high levels of Syk.…”

Section: Introductionmentioning

confidence: 99%

“…These data may appear to be somewhat in contradiction with previous studies reporting similar affinities of the ZAP-70 and Syk proteins for the various TCR ITAMs. [31][32][33] Nevertheless, the aforementioned studies were performed in vitro with peptide ITAMs and not in a cellular context where many other variables come into play.In addition to an inferior recruitment of Syk to the TCR-chain following CD3 engagement, it is also important to note that -associated Syk was poorly tyrosine phosphorylated. In accord with these data, phospho-Syk/TCR complexes have been difficult or impossible to detect in various T-cell models, even under conditions where both TCR-and Syk were highly phosphorylated.…”

mentioning

confidence: 99%

See 1 more Smart Citation

T-cell receptor–induced phosphorylation of the ζ chain is efficiently promoted by ZAP-70 but not Syk

Steinberg

Adjali

Swainson

et al. 2004

Blood

View full text Add to dashboard Cite

Engagement of the T-cell receptor (TCR)results IntroductionT-cell immune responses are coupled to activation of the T-cell receptor (TCR). Stimulation of this receptor results in the activation of signal transduction pathways, culminating in expression of cytokines and cellular proliferation. 1 Current models of antigen/ major histocompatibility complex (MHC)-induced T-cell activation are presented as ordered events with a sequential interaction of Src and ZAP-70/Syk protein tyrosine kinases (PTKs) with the TCR/CD3/ complex. Specifically, TCR engagement activates the Src family PTKs Lck/Fyn, which phosphorylate the tyrosines present in the immunoreceptor tyrosine activation motif (ITAM) [2][3][4] conserved in the CD3 and subunits of the TCR complex. 5,6 The ZAP-70/Syk PTKs then bind to the phosphorylated ITAMs via their respective SH2 domains, allowing their activation. 2,7,8 Once activated, ZAP-70/Syk kinases phosphorylate downstream, signaling intermediates such as Vav, Lat, and SLP-76 that are required for appropriate recruitment of downstream signaling cascades.ZAP-70 and Syk are structurally homologous; both proteins are composed of 2 tandemly arranged Src homology 2 (SH2) domains and a carboxy-terminal kinase domain. 7,9 Overall, these 2 kinases share more than 50% sequence identity with conserved tyrosine and serine phosphorylation sites. Although these 2 PTKs have some overlapping functions, 1 it has been hypothesized that in vivo, they are nonredundant because of their distinct expression profiles. ZAP-70 was initially reported to be expressed exclusively in thymocytes, T cells, and natural killer (NK) cells, whereas Syk was described as being expressed in a wide variety of hematopoietic cells but in only low levels in peripheral T cells. 10 Nevertheless, it has since been shown that Syk is expressed at high levels in human CD4 ϩ effector T cells and a subpopulation of TCR-stimulated ␣␤ T cells. 1,11 Moreover, the expression of Syk is not limited to hematopoietic cells, as it has been detected in vascular endothelial cells, 12 in epithelial cells, and in breast tissue. 13 With regard to ZAP-70, this PTK now has been shown to be expressed throughout normal B-cell development, at least in mice. 14 In humans, ZAP-70 has recently been detected in a subset of chronic lymphocytic leukemia (CLL) B cells, and importantly, its expression has been correlated with a poor prognosis. [15][16][17] The increased phosphorylation of Syk in ZAP-70-expressing CLL cells was the first indication that ZAP-70 may modulate the activity of Syk 18,19 rather than vice versa. Indeed, until these recent data were reported, Syk was assumed to be "superior" to ZAP-70, as its kinase activity is 100-fold higher than that of 20 it can be activated in an Lck-independent fashion, 21-25 and TCR-induced calcium flux is higher in the presence of Syk than 27 It has previously been shown that both Syk and ZAP-70 bind to Lck [28][29][30] and that in vitro, the 2 kinases bind to chain ITAMs with similar affinities. 31-33 Indeed, it has been hypo...

show abstract

“…The truncated protein would have cellular activating properties, in contrast with its ITIM-bearing counterpart which would inhibit cell signaling through recruitment of SHP-1, SHP-2, or SHIP phosphatases (9) seemingly via their respective carboxyl-terminal SH2 domains (12,13). Human immunoreceptors map to the "complex" or "leukocyte receptor cluster" located on chromosome region 19q13.4 or to the natural killer complex on chromosome 12 (11).…”

mentioning

confidence: 99%

PILRα, a Novel Immunoreceptor Tyrosine-based Inhibitory Motif-bearing Protein, Recruits SHP-1 upon Tyrosine Phosphorylation and Is Paired with the Truncated Counterpart PILRβ

Mousseau¹,

Banville²,

L’Abbé³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

SHP-1-mediated dephosphorylation of protein tyrosine residues is central to the regulation of several cell signaling pathways, the specificity of which is dictated by the intrinsic affinity of SH2 domains for the flanking sequences of phosphotyrosine residues. By using a modified yeast two-hybrid system and SHP-1 as bait, we have cloned a human cDNA, PILR␣, encoding a 303-amino acid immunoglobulin-like transmembrane receptor bearing two cytoplasmic tyrosines positioned within an immunoreceptor tyrosine-based inhibitory motif. Substrate trapping in combination with pervanadate treatment of 293T cells confirms that PILR␣ associates with SHP-1 in vivo upon tyrosine phosphorylation. Mutation of the tyrosine residues in PILR␣ indicates the pivotal role of the Tyr-269 residue in recruiting SHP-1. Surface plasmon resonance analysis further suggests that the association between PILR␣-Tyr-269 and SHP-1 is mediated primarily via the amino-terminal SH2 domain of the latter. Polymerase chain reaction amplification of cDNA in combination with genomic sequence analysis revealed a second gene, PILR␤, coding for a putative activating receptor as suggested by a truncated cytoplasmic tail and a charged lysine residue in its transmembrane region. The PILR␣ and PILR␤ genes are localized to chromosome 7 which is in contrast with the mapping of known members of the inhibitory receptor superfamily.

show abstract

Analysis of immunoreceptor tyrosine‐based activation motif (ITAM) binding to ZAP‐70 by surface plasmon resonance

Cited by 24 publications

References 23 publications

Gene Structure, Expression Pattern, and Biological Activity of Mouse Killer Cell Activating Receptor-associated Protein (KARAP)/DAP-12

Gene Structure, Expression Pattern, and Biological Activity of Mouse Killer Cell Activating Receptor-associated Protein (KARAP)/DAP-12

T-cell receptor–induced phosphorylation of the ζ chain is efficiently promoted by ZAP-70 but not Syk

PILRα, a Novel Immunoreceptor Tyrosine-based Inhibitory Motif-bearing Protein, Recruits SHP-1 upon Tyrosine Phosphorylation and Is Paired with the Truncated Counterpart PILRβ

Contact Info

Product

Resources

About