The fibronectin-derived anti-adhesive peptide III14-2 suppresses adhesion and apoptosis of leukemic cell lines through down-regulation of protein-tyrosine phosphorylation

We previously found that fibronectin (FN) has a cryptic functional site (YT IYVIAL, #1848-1855) opposing to cell adhesion to extracellular matrix (ECM) . The present study demonstrates that the FN peptide containing this anti-a dhesive site, termed peptide III14-2, affects programmed cell death (PCD) ( apoptosis) as well as cell adhesion by down-regulating protein-tyrosine pho sphorylation. Peptide III14-2 suppressed the integrin alpha 5 beta 1-mediat ed adhesion of leukemic cell lines (W562 and HL60), and protein tyrosine ph osphatase inhibitor, 1 mu M phenylarsine oxide (PAO) blocked the anti-adhes ive effect of peptide III14-2, These leukemic cells underwent PCD when expo sed to PAO at the higher concentration (5 mu M), as judged by nuclear and D NA fragmentations, and which was reversed by tyrosine kinase inhibitor, gen istein, Peptide III14-2 suppressed the PAO-induced PCD, whereas a control p eptide in which the anti-adhesive sequence YTIYVIAL is scrambled, was inact ive, Western blotting showed that PAO stimulated the tyrosine phosphorylati on of cellular proteins including focal adhesion kinase and that peptide II I14-2 inhibited them, suggesting that protein-tyrosine phosphorylation repr esents a common early signal for the adhesion and PCD. The anti-adhesive si te of FN molecule may play a crucial role also in a variety of cellular pro cesses other than adhesion and PCD by down-regulating protein-tyrosine phos phorylation.