Disease relevance of YWHAQ

• In this study we investigated whether the 1C5 transcript (YWHAQ) isolated from spinal cord was involved in amyotrophic lateral sclerosis (ALS) [1].
• HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses [2].
• New monoclonal antibody, 1C5, reactive with human cervical adenocarcinoma of the uterus, with immunodiagnostic potential [3].
• However, 1C5 did not show any reactivity to ectocervix epithelium, cervical intraepithelial neoplasia, or squamous cell carcinoma of the uterine cervix [3].
• As less than 3% of normal blood lymphocytes reacted with 1C5/B we suggest that the conversion to positivity may be a characteristic feature of the leukemic T-cell phenotype in Sézary syndrome [4].

High impact information on YWHAQ

• The HS1 protein is one of the major substrates of non-receptor-type protein-tyrosine kinases and is phosphorylated immediately after crosslinking of the surface IgM on B cells [5].
• Variants of WEHI-231 that were resistant to anti-IgM-induced apoptosis expressed dramatically reduced levels of HS1 protein [5].
• These results suggest that HS1 protein plays a crucial role in the B-cell antigen receptor-mediated signal transduction pathway that leads to apoptosis [5].
• Whereas many of the physical features of 3'HS1 are shared by 5'HS2 (a component of the 5' locus control region), transient expression studies show that 3' HS1 does not share the erythroid-specific enhancer activity exhibited by 5'HS2 [6].
• In addition, adenocarcinoma of the uterine cervix exhibited strong cytoplasmic reactivity with 1C5, whereas endometrial carcinoma of the uterus showed the luminal reactivity [3].

Biological context of YWHAQ

• These results show the marked up-regulation of the 14-3-3 isoform (YWHAQ) in ALS spinal cord and indicate the involvement of a potential 14-3-3-mediated survival pathway in the pathogenesis of ALS [1].
• The localisation of 1C5 (YWHAQ) to chromosome 2 was determined and coincides with that reported for clone HS1 (EMBL accession no. X57347) [1].
• We have recently isolated a 2.2-kb cDNA clone (1C5) from a human spinal cord cDNA library with partial identity to the 14-3-3 protein mRNA encoding the theta protein (YWHAQ) [1].
• Our data indicate that the proline-rich region of HS1 bordered by tyrosyl residues affected by Syk and Src family kinases represents a functional domain designed to undergo a process of sequential phosphorylation [7].
• Furthermore, activation-dependent tyrosine phosphorylation of HS1 was not required for NFAT transcriptional activation [8].

Anatomical context of YWHAQ

• Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling [9].
• Expression of the human HS1 protein from an expression vector introduced into one of the variant cell lines restored the sensitivity of the cells to apoptosis induced by surface IgM crosslinking [5].
• Additionally, no tyrosine phosphorylation of HS1 was induced by mitogenic pairs of anti-CD2 mAbs capable of activating the transcription factor NFAT (nuclear factor of activated T cells) [8].
• All together these results indicate that HS1 Tyr phosphorylation catalyzed by Syk and Lyn plays a crucial role in the translocation of the protein to the membrane and is involved in the cytoskeleton rearrangement triggered by thrombin in human platelets [10].
• Immunofluorescence microscopic analysis shows that the agonist promotes HS1 migration to the plasma membrane and that the inhibition of Lyn-mediated secondary phosphorylation of HS1 abrogates the subcellular translocation of the protein [10].

Associations of YWHAQ with chemical compounds

• 1C5 recognizes the region 119-130 corresponding to the GXXXG motif, the glycine zipper region, conserved in all mammals [11].
• By means of specific inhibitors (PP2, SU6656, and piceatannol) and phosphopeptide-specific antibodies, as well as by coimmunoprecipitation and binding competition experiments, we show that Syk acts as the primary kinase that phosphorylates HS1 at Tyr397 and that Syk phosphorylation is required for HS1 interaction with the Lyn SH2 domain [10].
• 1C5 can be used for the staining of routine formalin-fixed and paraffin-embedded tissue sections [3].
• 1C5 also reacts with 95% ethanol-fixed malignant cells in cervical smears [3].
• Related studies have shown that citrate removed calcium bound by PPG; N6-substituted adenines were bound by PPG while three polyphosphorylated dinucleosides, HS3, HS2, and HS1, were displaced from it [12].

Other interactions of YWHAQ

• Costimulation through CD28 and/or CD2 did not modulate the CD3-dependent phosphorylation of HS1 [8].
• Uncoupling activation-dependent HS1 phosphorylation from nuclear factor of activated T cells transcriptional activation in Jurkat T cells: differential signaling through CD3 and the costimulatory receptors CD2 and CD28 [8].
• Ligation of CD3 also induces the tyrosine phosphorylation of HS1, a 75-kDa hematopoietic cell-specific intracellular signaling protein of unknown function [8].
• Molecular features underlying the sequential phosphorylation of HS1 protein and its association with c-Fgr protein-tyrosine kinase [7].
• Observed changes in 5-(((acetylamino)ethyl)amino) naphthalene-1-sulfonic acid fluorescence strongly suggest physical contacts between the 14-3-3 protein and labeled parts of the FOXO4 DNA binding interface [13].

Analytical, diagnostic and therapeutic context of YWHAQ

• Both devices (the Philips FR2 or the HS1) are used in public access defibrillator settings [14].
• After full length determination by PCR, HS-1 gene was found to be composed of two exons, separated by an intron [15].
• Immunohistochemical comparison of new monoclonal antibody 1C5 and carcinoembryonic antigen in the differential diagnosis of adenocarcinoma of the uterine cervix [16].

References