Disease relevance of SKAP2

• Unlike SKAP55, which is specifically expressed in thymus and T cells, RA70 was expressed ubiquitously in various tissues including lung, skeletal muscle, and spleen, and in various cell lines including human monocytic leukemia (U937) cells, but RA70 was undetectable in thymus and T cell lymphoma (Jurkat) cells [1].
• It would appear that HIV proteinase inhibitors also have a direct effect on one of the key virulence factors of C. albicans, the secreted aspartic proteinases (Saps) [2].
• The lower rates of oropharyngeal candidiasis observed in individuals receiving antiretroviral combination therapy could reflect not only an improvement in the immune system but also direct inhibition of Candida Saps by HIV protease inhibitors [3].

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

• Electrophoretic mobility shift assays demonstrated that NF-Y bound to the CCAAT element of both SKAP55R and junB [7].

References