Grap Negatively Regulates T-Cell Receptor-Elicited Lymphocyte Proliferation and Interleukin-2 Induction

Shen, Rongkun; Ouyang, Ying; Qu, Cheng Kui; Alonso, Andrés; Sperzel, Lindsey; Mustelin, Tomas; Kaplan, Mark H.; Feng, Gen Sheng

doi:10.1128/mcb.22.10.3230-3236.2002

Cited by 45 publications

(31 citation statements)

References 49 publications

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“…It also associates with LAT through its SH2 domain (Trub et al 1997;Zhang et al 1998a). Studies of T cells from Grap-deficient mice indicate that Grap may be a negative regulator of TCR signal transduction (Shen et al 2002).…”

Section: Plc-g1 Binds Y132 Of Lat and Mediates Transcriptional Activamentioning

confidence: 99%

The LAT Story: A Tale of Cooperativity, Coordination, and Choreography

Balagopalan¹,

Coussens²,

Sherman³

et al. 2010

Cold Spring Harbor Perspectives in Biology

150

184

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The adapter molecule LAT is a nucleating site for multiprotein signaling complexes that are vital for the function and differentiation of T cells. Extensive investigation of LAT in multiple experimental systems has led to an integrated understanding of the formation, composition, regulation, dynamic movement, and function of LAT-nucleated signaling complexes. This review discusses interactions of signaling molecules that bind directly or indirectly to LAT and the role of cooperativity in stabilizing LAT-nucleated signaling complexes. In addition, it focuses on how imaging studies visualize signaling assemblies as signaling clusters and demonstrate their dynamic nature and cellular fate. Finally, this review explores the function of LAT based on the interpretation of mouse models using various LAT mutants.

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Section: Plc-g1 Binds Y132 Of Lat and Mediates Transcriptional Activamentioning

confidence: 99%

The LAT Story: A Tale of Cooperativity, Coordination, and Choreography

Balagopalan¹,

Coussens²,

Sherman³

et al. 2010

Cold Spring Harbor Perspectives in Biology

150

184

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“…Gads and Grap, by contrast, are highly restricted in their expression to a subset of immune cells and appear to function primarily in signalling downstream of the T-cell and B-cell receptors. Loss of Grb2 results in embryonic lethality [25], whereas loss of Gads or Grap leads to rather specific immune phenotypes [26,27]. While the three encoded genes are closely related, they possess distinct roles in their specific cellular context.…”

Section: Sh2 Domains Have a Broad Role In Phosphotyrosine Signalling mentioning

confidence: 99%

Evolution of SH2 domains and phosphotyrosine signalling networks

Liu

Nash

2012

Phil. Trans. R. Soc. B

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Src homology 2 (SH2) domains mediate selective protein-protein interactions with tyrosine phosphorylated proteins, and in doing so define specificity of phosphotyrosine (pTyr) signalling networks. SH2 domains and protein-tyrosine phosphatases expand alongside protein-tyrosine kinases (PTKs) to coordinate cellular and organismal complexity in the evolution of the unikont branch of the eukaryotes. Examination of conserved families of PTKs and SH2 domain proteins provides fiduciary marks that trace the evolutionary landscape for the development of complex cellular systems in the proto-metazoan and metazoan lineages. The evolutionary provenance of conserved SH2 and PTK families reveals the mechanisms by which diversity is achieved through adaptations in tissue-specific gene transcription, altered ligand binding, insertions of linear motifs and the gain or loss of domains following gene duplication. We discuss mechanisms by which pTyr-mediated signalling networks evolve through the development of novel and expanded families of SH2 domain proteins and the elaboration of connections between pTyr-signalling proteins. These changes underlie the variety of general and specific signalling networks that give rise to tissue-specific functions and increasingly complex developmental programmes. Examination of SH2 domains from an evolutionary perspective provides insight into the process by which evolutionary expansion and modification of molecular protein interaction domain proteins permits the development of novel protein-interaction networks and accommodates adaptation of signalling networks.

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“…Grb2 associates with a variety of molecules via its N-terminal SH3 domain, and, interestingly, Grap associates with only some molecules among Grb2 partners (45). It was recently reported that Rasdependent T cell proliferation and IL-2 production were enhanced in Grap-deficient mice (47), suggesting that Grap itself could mediate negative regulation. When recruited by Fc␥RIIB, adapters may thus reinforce inhibition.…”

Section: Fig 5 the Two Tyrosine-based Motifs Cooperate To Bind Ship1mentioning

confidence: 99%

Two Distinct Tyrosine-based Motifs Enable the Inhibitory Receptor FcγRIIB to Cooperatively Recruit the Inositol Phosphatases SHIP1/2 and the Adapters Grb2/Grap

Isnardi

Lesourne

Bruhns

et al. 2004

Journal of Biological Chemistry

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Fc␥RIIB are low-affinity receptors for IgG that contain an immunoreceptor tyrosine-based inhibition motif (ITIM) and inhibit immunoreceptor tyrosine-based activation motif (ITAM)-dependent cell activation. When coaggregated with ITAM-bearing receptors, Fc␥RIIB become tyrosyl-phosphorylated and recruit the Src homology 2 (SH2) domain-containing inositol 5-phosphatases SHIP1 and SHIP2, which mediate inhibition. The Fc␥RIIB ITIM was proposed to be necessary and sufficient for recruiting SHIP1/2. We show here that a second tyrosine-containing motif in the intracytoplasmic domain of Fc␥RIIB is required for SHIP1/2 to be coprecipitated with the receptor. This motif functions as a docking site for the SH2 domain-containing adapters Grb2 and Grap. These adapters interact via their C-terminal SH3 domain with SHIP1/2 to form a stable receptor-phosphatase-adapter trimolecular complex. Both Grb2 and Grap are required for an optimal coprecipitation of SHIP with Fc␥RIIB, but one adapter is sufficient for the phosphatase to coprecipitate in a detectable manner with the receptors. In addition to facilitating the recruitment of SHIPs, the second tyrosinebased motif may confer upon Fc␥RIIB the properties of scaffold proteins capable of altering the composition and stability of the signaling complexes generated following receptor engagement. (5), i.e. by all receptors containing immunoreceptor tyrosine-based activation motifs. Fc␥RIIB must be coaggregated with activating receptors via IgG immune complexes in order to exert their inhibitory effects (2). The in vivo relevance of the regulatory properties of Fc␥RIIB was ascertained in Fc␥RIIB-deficient mice. Fc␥RIIB Ϫ/Ϫ mice were shown to mount enhanced antibody responses (6), exhibit enhanced IgG-and IgE-induced anaphylactic reactions (7), be hypersensitive to collagen-induced arthritis (8, 9), and develop spontaneous systemic lupus erythematosus in the C57BL/6 background (10). Fc␥RIIB are therefore likely to play major roles in the prevention of autoimmune diseases, allergies, and other inflammatory diseases.The regulatory properties of Fc␥RIIB were shown to depend on the presence of an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its intracytoplasmic domain. This motif was defined as a tyrosine residue that is followed at position Tyr ϩ 3 and preceded at position Tyr Ϫ 2 by hydrophobic amino acids (11). The ITIM tyrosine becomes phosphorylated by a Src family protein tyrosine kinase upon the coaggregation of inhibitory receptors with activating receptors (12), providing a docking site for SH2 domain-containing cytosolic phosphatases (13). Because of the presence of a leucine residue at position Tyr ϩ 2 (14), Fc␥RIIB were shown to recruit selectively the single SH2 domain-containing inositol 5Ј-phosphatases SHIP1 (15, 16) and/or SHIP2 (17). These phosphatases dephosphorylate 5Ј-phosphate groups in 3Ј-phosphorylated inositols and phosphatidylinositides (18, 19) among which phosphatidylinositol 3,4,5-triphosphate (20, 21), generated by phosphatidylinositol 3-kinase duri...

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Grap Negatively Regulates T-Cell Receptor-Elicited Lymphocyte Proliferation and Interleukin-2 Induction

Cited by 45 publications

References 49 publications

The LAT Story: A Tale of Cooperativity, Coordination, and Choreography

The LAT Story: A Tale of Cooperativity, Coordination, and Choreography

Evolution of SH2 domains and phosphotyrosine signalling networks

Two Distinct Tyrosine-based Motifs Enable the Inhibitory Receptor FcγRIIB to Cooperatively Recruit the Inositol Phosphatases SHIP1/2 and the Adapters Grb2/Grap

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