Psychiatry related information on FYB

• This biochemical assay of ADAP may prove to be helpful as an adjunct in the clinicopathologic diagnosis of Alzheimer's disease [1].
• Clinical dementia, neuritic plaques, and old age per se are not correlated with increased ADAP levels [1].

High impact information on FYB

• The normal control and neurologic disease control cases had essentially no detectable level of ADAP, while ADAP was clearly detected in 85.7% of the Alzheimer's disease cases [1].
• Recently the adapter protein ADAP/Fyb/Slap has been shown to couple TCR stimulation to integrin activation by mediating increased integrin avidity [2].
• Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP [3].
• Here, we show that upon activation of Jurkat cells microtubules project from the MTOC to a ring of the scaffolding protein ADAP, localized at the synapse [4].
• ADAP coprecipitates with dynein from activated Jurkat cells, and loss of ADAP prevents MTOC translocation and the specific recruitment of dynein to the synapse [4].

Biological context of FYB

• Finally, fluorescence in situ hybridization analysis localized the FYB gene to human chromosome 5 at position p13 [5].
• FcepsilonRI aggregation increased FYB tyrosine phosphorylation, whereas confocal immunofluorescence microscopy showed that FYB colocalizes with F-actin in membrane ruffles and plaques [6].
• The regulation of these two events could be distinguished from each other by the requirement of the FYB SH3 domain in beta-hexosaminidase release, but not adhesion, and the up-regulation of mediator release by FYB in nonadherent cells [6].
• These data suggest that SLP-76 recruits a negative regulator, SLAP-130, as well as positive regulators of signal transduction in T cells [7].
• FYA, FYB, FYB(ES), and FYB(WK) are the alleles; Fy(a+b-), Fy(a-b+), Fy(a+b+), Fy(a-b+(wK)), and Fy(a-b-), are the phenotypes, and Fy(a), Fy(b), Fy3, Fy5, and Fy6 are the antigens [8].

Anatomical context of FYB

• In keeping with this, expression of FYB augmented interleukin 2 secretion from a T cell hybridoma, DC27.10, in response to TcRzeta/CD3 ligation [9].
• Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production [9].
• Our findings identify FYB as a regulator of integrin-mediated adhesion and degranulation events, which, in the case of mast cells, has potential applications to inflammatory and allergic responses [6].
• We establish that SKAP55 and SLAP-130 associate with each other when both molecules are co-expressed in COS cells [10].
• In the context of T cell signalling, our findings suggest that ADAP, upon recruitment to the cell-cell junction as part of a multiprotein complex, directly interacts with phosphoinositide-enriched regions of the plasma membrane [11].

Associations of FYB with chemical compounds

• Recently ADAP was shown genetically to positively regulate T cell activation, TCR-induced integrin clustering, and T cell adhesion [12].
• While primary binding occurs via SKAP-55 SH3 domain binding to a proline-rich region in ADAP, a second interaction occurs between the ADAP C-terminal SH3 domain (ADAP-SH3c) and a non-canonical RKXXY(294)XXY(297) motif in SKAP-55 [13].
• ADAP levels in four regions of AD brains were not correlated to neuritic plaque count in corresponding regions of matching formaldehyde-fixed hemispheres [14].

Physical interactions of FYB

• FYB/SLAP has the hallmarks of an adaptor protein that binds to the SH2 domains of the Src kinase FYN-T and SLP-76 [5].
• Finally, we demonstrate that, as previously shown for SKAP55, SKAP-HOM interacts with the recently identified polypeptide SLAP-130 [15].

Regulatory relationships of FYB

• 1. FYB-130 therefore represents a novel variant of FYB protein that can up-regulate T-cell receptor-driven interleukin 2 production in mature T-cells [5].
• In this study, we demonstrate that FYB can up-regulate integrin-mediated adhesion to fibronectin and mediator release in RBL-2H3 mast cells [6].

Other interactions of FYB

• Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases [7].
• We demonstrate that SLAP-130 is hematopoietic cell-specific and associates with the SH2 domain of SLP-76 [7].
• In this study, using a two-hybrid screen with FYB as bait, we have identified eight clones, four of which correspond to the recently published lymphoid protein SKAP55, and two which correspond to a related protein with some 44% homology to SKAP55 (termed SKAP55-related protein, SKAP55R) [16].
• The effect of SLAP-130 on SLP-76 function is specific for regulating TCR-induced ERK activation, but not phospholipase Cgamma 1 phosphorylation [17].
• We also identified and validated three genes [(natural cytotoxicity triggering receptor (NCR)3, fucosyl transferase (FUT)4 and Fyn-binding protein (FYB)] that had not been shown to have significant cyclic changes in the human endometrium, previously [18].

Analytical, diagnostic and therapeutic context of FYB

• Here we describe the molecular cloning of SLAP-130, a SLP-76-associated phosphoprotein of 130 kDa [7].
• Furthermore, immunofluorescence confocal microscopy showed that FYB and SKAP55 colocalize in the perinuclear region of cells [16].
• A concordance rate of 100 per cent was observed between serotyping and ASPCR detection of the FYA, FYB and nullFY alleles [19].
• The concentration of Alzheimer's disease-associated protein (ADAP) was measured in postmortem brain tissue samples of temporal or frontal cortex from 111 human brains using a sandwich immunoassay [1].
• Crossed affinity immunoelectrophoresis was used to estimate the binding constant for the interaction of PHF-1 with ADAP and to estimate the fraction of PHF-1 reactive protein [20].

References