Inhibition of pp125FAK in cultured fibroblasts results in apoptosis.

Abstract

Abstract. The tyrosine kinase called pp125 FAK is believed to play an important role in integrin-mediated signal transduction, pp125 FAK is associated both functionally and spatially with integrins, which are the cell surface receptors for extracellular matrix components. Although the precise function of pp125 FAK is not known, two possibilities have been proposed: pp125 yAK may regulate the assembly of focal adhesions in spreading or migrating cells, or pp125 FAK may participate in a signal transduction cascade to inform the nucleus that the cell is anchored. To test these models in living cells, a peptide representing the focal adhesion kinase (FAK)-binding site of the 131 tail was coupled to carrier protein and injected into cultured cells to competitively inhibit the binding of pp125 FAK to endogenous integrin, thus inhibiting activation of pp125 FAK on a cell-by-cell basis. In addition, an antibody directed against an epitope adjacent to the focal adhesion targeting sequence on pp125 FAK was microinjected, as an alternative means of inhibiting pp125 FAK activation. It was observed that when rounded cells were injected with either the integrin peptide or the anti-FAK antibody, the cells rapidly began to apoptose, within 4 h after injection. These results indicate that pp125 FA~ may play a critical role in suppressing apoptosis in fibroblasts.

In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance

“…In these studies the role of FAK was not evaluated. However, other studies demonstrated that antisense or antibodymediated FAK inhibition results in increased apoptosis [62] and provided a link between integrin signaling, FAK activation and Bcl-2 up-regulation via PI3 K and Akt [63][64][65]. In line with these findings, apoptosis resistance of AA LNC was strengthened by CD3 plus CD44 or CD49d cross-linking.…”

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

“…This effect was dependent upon both FAK kinase activity and its phosphorylation on tyrosine 397. Other studies have shown that disrupting FAK signalling using anti-FAK antibodies, antisense oligonucleotides, or the expression of dominant-negative FAK, induces apoptosis in adherent cells (Gilmore et al, 2000;Hungerford et al, 1996;Ilic et al, 1998;Xu et al, 1996;Xu et al, 1998). Moreover, genetic deletion of FAK sensitises keratinocytes and endothelial cells to apoptosis in vivo (Braren et al, 2006;Essayem et al, 2006).…”

Differential FAK phosphorylation at Ser-910, Ser-843 and Tyr-397 induced by angiotensin II, LPA and EGF in intestinal epithelial cells

“…This model of FAK activation and Tyr-397 phosphorylation is thought to be of central importance for FAKdependent signaling. The biological importance of FAK-mediated signal transduction is underscored by the fact that this tyrosine kinase plays a fundamental role in embryonic development [11,12] and in the control of cell migration [9,[12][13][14][15][16][17][18][19], cell cycle progression [20] and apoptosis [21][22][23][24]. Furthermore, there is increasing evidence linking overexpression of FAK to the invasive properties of cancer cells [25][26][27][28][29][30][31].…”