SETA (also known as CIN85 or Ruk) is an SH3-domain-containing adaptor protein that functions in several signalling pathways – for example, it regulates PI 3-kinase (PI3K) signalling by interacting with the PI3K regulatory subunit p85α and facilitates internalization of receptor tyrosine kinases by binding to the ubiquitin ligase Cbl. Oliver Bögler and co-workers have found that SETA has another string to its bow: it's involved in cell adhesion (see ). Using confocal microscopy, they observe that SETA co-localizes with actin along microfilaments and at focal adhesions, as well as with microtubules. The protein does not interact with cytoskeletal filaments directly; instead these interactions are mediated by the SETA partner AIP1, which the authors show binds strongly to actin and tubulin. Bögler and co-workers can also identify SETA and AIP1 in complexes containing focal adhesion kinase (FAK) and its relative PYK2. Moreover, they demonstrate that SETA and AIP1 can regulate cell adhesion in electrical cell-substrate sensor (ECIS) attachment assays and that AIP1 attenuates FAK/PYK2 phosphorylation. The authors thus conclude that SETA and AIP1 can regulate cell adhesion, suggesting they do so as part of a focal adhesion kinase regulatory complex.
