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SKAP2  -  src kinase associated phosphoprotein 2

Homo sapiens

Synonyms: PRAP, Pyk2/RAFTK-associated protein, RA70, Retinoic acid-induced protein 70, SAPS, ...
 
 
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Disease relevance of SKAP2

 

High impact information on SKAP2

  • Both SKAP55 and SKAP55R were found to bind FYB through their SH3 domains and to act as substrates for the FYN kinase in T cells [4].
  • Such phosphorylation was inhibited by PRAP expression, suggesting that PRAP negatively regulates alpha-synuclein phosphorylation following cell stress [5].
  • PRAP was observed to be present throughout the brain, including substantia nigra dopaminergic neurons, in which it localized to the cytoplasm [5].
  • These data show that the potential of specific Saps to cause tissue damage correlates with an epithelium-induced proinflammatory cytokine response, which may be crucial in controlling and managing C. albicans infections at the vaginal mucosa in vivo [6].
  • Furthermore, enforced over-expression of SKAP55R in primary bone marrow cells inhibited colony growth [7].
 

Anatomical context of SKAP2

  • Thus, unlike SKAP55, which is exclusively expressed in T lymphocytes, SKAP-HOM expression is ubiquitous [8].
  • In addition, SKAP-HOM does not associate with p59fyn in T cells although it represents a specific substrate for the kinase in COS cells [8].
  • In macrophages additional substrates have been found, the Fyn-binding/SLP-76-associated protein and SKAP-HOM [9].
  • Sap immunoreactivity can be detected in particular at the site of close contact between C. albicans and epithelial cells, suggesting a pathogenetic role of the Saps in host-fungal interaction [10].
  • In this study, we have identified the cis-acting elements that control SKAP55R transcription in myeloid cells [7].
 

Associations of SKAP2 with chemical compounds

  • Furthermore, while SKAP55 is constitutively tyrosine phosphorylated in resting human T cells, SKAP-HOM is expressed as a non-phosphorylated protein in the absence of external stimulus but becomes phosphorylated following T cell activation [8].
  • Western blots analysis was performed using antibodies against the pro-caspase-3, or PRAP (Poly (ADP-ribose) polymerase).The results showed that delta-elemene exhibited a marked antiproliferative effect on Hela cells in dose- and time-dependent manners, and had little inhibition to normal human liver cell line WRL-68 [11].
 

Physical interactions of SKAP2

  • Finally, we demonstrate that, as previously shown for SKAP55, SKAP-HOM interacts with the recently identified polypeptide SLAP-130 [8].
 

Other interactions of SKAP2

  • SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55 [8].
  • 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) [4].
 

Analytical, diagnostic and therapeutic context of SKAP2

References

  1. RA70 is a src kinase-associated protein expressed ubiquitously. Kouroku, Y., Soyama, A., Fujita, E., Urase, K., Tsukahara, T., Momoi, T. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  2. Anti-fungal therapy at the HAART of viral therapy. Munro, C.A., Hube, B. Trends Microbiol. (2002) [Pubmed]
  3. Secreted aspartic proteases as virulence factors of Candida species. Monod, M., Borg-von, Z.M. Biol. Chem. (2002) [Pubmed]
  4. FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells. Liu, J., Kang, H., Raab, M., da Silva, A.J., Kraeft, S.K., Rudd, C.E. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation. Takahashi, T., Yamashita, H., Nagano, Y., Nakamura, T., Ohmori, H., Avraham, H., Avraham, S., Yasuda, M., Matsumoto, M. J. Biol. Chem. (2003) [Pubmed]
  6. Candida albicans-secreted aspartic proteinases modify the epithelial cytokine response in an in vitro model of vaginal candidiasis. Schaller, M., Korting, H.C., Borelli, C., Hamm, G., Hube, B. Infect. Immun. (2005) [Pubmed]
  7. NF-Y regulates LIF-induced transcription of the signaling adaptor SKAP55R in myeloid cells. Curtis, D.J., Dougherty, L., Bodine, D.M. Leukemia (2001) [Pubmed]
  8. SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55. Marie-Cardine, A., Verhagen, A.M., Eckerskorn, C., Schraven, B. FEBS Lett. (1998) [Pubmed]
  9. Resistance to phagocytosis by Yersinia. Fällman, M., Deleuil, F., McGee, K. Int. J. Med. Microbiol. (2002) [Pubmed]
  10. In vivo expression and localization of Candida albicans secreted aspartyl proteinases during oral candidiasis in HIV-infected patients. Schaller, M., Hube, B., Ollert, M.W., Schäfer, W., Borg-von Zepelin, M., Thoma-Greber, E., Korting, H.C. J. Invest. Dermatol. (1999) [Pubmed]
  11. The Effect of delta-Elemene on Hela Cell Lines by Apoptosis Induction. Wang, X.S., Yang, W., Tao, S.J., Li, K., Li, M., Dong, J.H., Wang, M.W. Yakugaku Zasshi (2006) [Pubmed]
 
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