Disease relevance of IGSF8

• Overexpression of EWI-2 in A431 epidermoid carcinoma cells did not alter cell adhesion or spreading on laminin-5, and had no effect on reaggregation of cells plated on collagen I (alpha2beta1 integrin ligand) [1].

High impact information on IGSF8

• CD81 also controlled EWI-2 maturation and cell surface localization [1].
• EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5 [1].
• In contrast, an EWI-2 chimeric mutant failed to suppress cell migration, redirect CD81 to filopodia, or enhance alpha3beta1-CD81 complex formation [1].
• These results show how laterally associated EWI-2 might regulate alpha3beta1 function in disease and development, and demonstrate how tetraspanin proteins can assemble multiple nontetraspanin proteins into functional complexes [1].
• EWI-2 modulates lymphocyte integrin alpha4beta1 functions [2].

Biological context of IGSF8

• Functionally, silencing of endogenous EWI-2 expression by short interfering RNA in lymphoid CEM cells augmented cell migration, cellular polarity, and increased phosphorylation of ERMs [3].
• EWI-2 overexpression not only suppressed cell migration, but also redirected CD81 to cell filopodia and enhanced alpha3beta1-CD81 complex formation [1].
• Ligand-induced receptor down-regulation (LIRD) was impaired in mutant-expressing cells [4].

Anatomical context of IGSF8

• Confocal microscopy analysis revealed that EWI-2 and EWI-F colocalized with ERM proteins at microspikes and microvilli of adherent cells and at the cellular uropod in polarized migrating leukocytes [3].
• EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins [3].
• Although it remains to be determined whether PGRL possesses PG regulatory functions, transwell chamber experiments show that PGs and CD81 coordinately regulate T cell motility [5].

Associations of IGSF8 with chemical compounds

• Inhibition of HSP90 activity with geldanamycin restored Cbl function as indicated by receptor ubiquitination and LIRD [4].

Physical interactions of IGSF8

• Soluble EWI-2 bound both to cells expressing HSPA8 and also to immobilized HSPA8 protein [6].

Other interactions of IGSF8

• However, EWI-2 markedly impaired spreading and ruffling on VCAM-1 [2].

Analytical, diagnostic and therapeutic context of IGSF8

• Immunoprecipitation studies showed the association of EWI-2 and EWI-F with ERM proteins in vivo [3].

References