Adhesion Molecule Phosphorylation in Cancer Chemotherapy - Adhesion Molecules - page 343

As the cytoplasmic tails of the integrin receptors directly link to polymerized
actin i laments that critically determine cell structure, it was initially believed
that integrin receptors simply regulated cell structure. h e realization that a vast
array of signalling molecules are recruited to the receptors made it clear, however,
that integrins are important sites of signal transduction. Under light microscopy,
ligated and clustered integrin receptor complexes are visualized in cultured cells
as macromolecular structures with a dash-like morphology and these structures
are known as focal adhesions/contacts (Fig. 1) . h e integrin 'adhesome' has 156
components networked by up to 690 interactions (Zaidel-Bar et al. 2007).
Fig. 1 Paxillin-positive focal adhesions in cultured neuroblastoma cells. SHEP neuroblastoma
cells were processed for immunol uorescence analysis as previously described (Cowell et al. 2006)
and immunostained with anti-paxillin antibodies. Arrows indicate the large paxillin-positive focal
adhesions. Note also the punctate cytoplasmic staining, absent from the nucleus. Scale bar 10 μm.
(G. O. unpublished data.)
Integrin Receptor Stimulated Phosphorylation
Integrin receptors have no intrinsic enzymatic activity but instead recruit non-
receptor protein tyrosine kinases, such as FAK and Src family kinases, that catalyse
tyrosine phosphorylation (Fig. 2) . Phosphorylation of consensus tyrosine sites
creates binding sites for partner molecules, the most prevalent of which are those
containing Src-Homology 2 protein domains (SH2). Dif erent SH2 domains show
preference for binding to conserved phospho-peptide sequences, thus providing
specii city in the assemblage of signalling networks. SH2 domains are present
not only in proteins with intrinsic enzymatic activity (e.g., FAK and Src) but
also in adaptor proteins (e.g., paxillin and p130Cas) that interact with, and are