Disease relevance of Grap2

• Splenic immune suppression in sepsis: A role for IL-10-induced changes in P38 MAPK signaling [1].

High impact information on Grap2

• Requirement for the SLP-76 adaptor GADS in T cell development [2].
• A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined [2].
• After phosphorylation of the cytosolic domain of LAT, multiple signaling molecules such as phospholipase C-gamma1, Grb2, and Gads associate with phosphorylated LAT via their SH2 domains [3].
• Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region [4].
• We further demonstrated that the expression of the Gads-binding region of SLP-76 in bone marrow-derived mast cells inhibits FcepsilonRI-induced calcium flux, degranulation, and cytokine secretion [5].

Biological context of Grap2

• Regulation of BLNK recruitment was dependent upon the Grap2 proline-rich domain, while modulation of phosphorylation was dependent upon both the proline-rich and SH2 domains [6].
• The intracellular signaling pathways that regulate homeostasis in CD4(+) and CD8(+) T cells are clearly different, and the Gads adaptor protein is critical for homeostasis of CD4(+) T cells [7].
• Mapping experiments have revealed that the carboxyl-terminal SH3 domain of Gads and the fourth proline-rich region of HPK1 are essential for their interaction [8].
• Gads(-/-) CD4(+) T cells were markedly deficient in the spleen and had an activated phenotype and a rapid turnover rate [7].
• Gads(-/-) CD4(+) T cells, but not CD8(+) T cells, had a severe block of TCR-mediated proliferation and a high rate of spontaneous cell death and were highly susceptible to CD95-induced apoptosis [7].

Anatomical context of Grap2

• Thermal injury-induced priming effect of neutrophil is TNF-alpha and P38 dependent [9].
• Spi-1 and Spi-B control the expression of the Grap2 gene in B cells [6].
• Expression library screening for additional Gads-interacting molecules identified the hemopoietic progenitor kinase-1 (HPK1), and we investigated the HPK1-Gads interaction within the DO11.10 murine T cell hybridoma system [8].
• The Gads adaptor protein is expressed in many hematopoietic tissues, including bone marrow, lymph node, and spleen [10].
• Grb-2-related adaptor protein (Grap) is a Grb2-like SH3-SH2-SH3 adaptor protein with expression restricted to lymphoid tissues [11].

Associations of Grap2 with chemical compounds

• Our results demonstrate that HPK1 inducibly associates with Gads and becomes tyrosine phosphorylated following TCR activation [8].
• Inversely, in IC1LC131, Erk and Akt pathways remained active, while Jnk and P38 pathways were inhibited by gefitinib [12].
• P38 and activating transcription factor-2 involvement in osteoblast osmotic response to elevated extracellular glucose [13].

Regulatory relationships of Grap2

• Disruption of SLP-76 interaction with Gads inhibits dynamic clustering of SLP-76 and FcepsilonRI signaling in mast cells [5].

Other interactions of Grap2

• Gads(-/-) CD8(+) T cells had a memory-like phenotype, produced IFN-gamma in response to ex vivo stimulation, and underwent normal homeostatic proliferation in wild-type hosts [7].
• The regulation of the metabolic insulin response by mouse growth factor receptor-binding protein 10 (Grb10) has been addressed in this report [14].
• Recently, several new members of this family have been identified including IRS-3, IRS-4, and growth factor receptor-binding protein 2-associated binder-1 (Gab-1) [15].

Analytical, diagnostic and therapeutic context of Grap2

• Whereas BCR ligation can induce apoptosis in wild-type transitional stage 1 (T1) B cells, Gads(-/-) T1 B cells were resistant to BCR-induced apoptosis [10].

References