Intra- and intermolecular interactions mediated by adaptor protein Ruk/CIN85/SETA

• Published in: Biopolimery i kletka 2005, Vol.21 (1), p.48-54
• Main Authors: Ilnytska, O. M., Drel', V. R., Shuvayeva, H. Yu, Havrylov, S. V., Fedyshyn, Ya. Ya, Mayevska, O. M., Ihumentseva, N. I., Gout, I. T., Buchman, V. L., Drobot, L. B.
• Format: Article
• Language: English
• Subjects: Actin; Apoptosis; Cell adhesion; Cell adhesion & migration; Cytoskeleton; Evolutionary conservation; Isoforms; Kinases; Lymphocytes T; Oligomerization; Proline; Tyrosine
• ISSN: 0233-7657; 1993-6842
• DOI: 10.7124/bc.0006DB

Ruk/CIN85l SETA is a member of a separate and evolutionary conserved family of adapter I scaffold proteins implicated in apoptic and receptor tyrosine kinases signalling, rearrangement of actin cytoskeleton and cell adhesion, podocyte and T cell functions. Self-regulation through intra- and intercellular interactions can be supposed for RuklCIN85l SETA as this protein contains SH3 domains and proline-rich sequence, localized within one polypeptide chain, as well as C-terminal coiled-coil region. The ability of Ruk proline-rich motifs to interact with its own SH3 domains in an intramolecular fashion and coiled-coil region to mediate oligomerization between different isoforms was assessed in GST pull down experiments. It was shown that both Ruk SH3A and to a less extent SH3B domains can interact with its own proline-rich sequences in a cooperative manner, while coiled-coil region provide for isoforms oligomerization. SH3C domain appear exerts conformational constraints, imposed on coiled-coil region, restricting the level of oligomerization. We also demonstrated that the ability of exogenous ligands to interact with Ruk polyprotine motifs is changing during the course of TNFa-induced apoptosis of human myelomonocytic W37 cells.