Volume 120, Issue 1, Pages 294-298 (January 2001) Apoptosis—programmed cell death and its relevance to gastrointestinal epithelium: Survival signal from the matrix  Andrzej S. Tarnawski  Gastroenterology  Volume 120, Issue 1, Pages 294-298 (January 2001) DOI: 10.1053/gast.2001.21402 Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 1 (A) Signaling pathways of apoptosis. Activation of cell surface death factor receptors (TNFR1, CD95/Fas receptor) by TNF-α or CD95L/FasL leads to receptor oligomerization, recruitment of adaptor proteins, and activation of initiator caspases -8, -9, or -10. JNK1/SAPK and p38 kinase signal transduction pathways are involved in some steps of this process. Initiator caspases trigger activation of executioner caspases (-3, -6, and -7). In mitochondrial pathway, the release of cytochrome c by proapoptotic stimuli leads to its binding to APAF-1 and activation of procaspase-9, which in turn triggers the activation of executioner caspases. Activated executioner caspases cleave the nuclear and cytoskeletal proteins, leading to morphologic changes characteristic for apoptosis (Table 1) and ultimately to cell death. (B) Attachment of cells to the matrix occurs via focal adhesions. The integrin-triggered signals from the matrix are mediated via recruitment of focal adhesion proteins such as FAK, paxillin, Scr, vinculin, β-catenin, α-actinin, and p130Cas proximal to the cytoplasmic tail of β1-integrins. Focal adhesions are important for prosurvival signaling through PI-3K and Akt signal transduction pathways, NF-κB activation, and induction of IAPs. Akt, serine/threonine kinase also known as protein kinase B; APAF-1, apoptosis protease activator protein 1; CD95L/FasL, CD95 ligand or Fas ligand; FADD/MORT1 Fas-associated death domain protein; FAK, focal adhesion kinase; IAP, inhibitor of apoptosis protein; JNK1/SAPK, C-Jun N-terminal kinase or stress activated protein kinase; NF-κB, nuclear factor–κB; PARP, poly(ADP-ribose) polymerase; PI-3K, phosphatidylinositol-3 kinase; RAIDD, RIP-associated protein with death domain; Rb, retinoblastoma protein; RIP, receptor interacting protein; STAT1, signal transducer and activator of transcription 1; TNF, tumor necrosis factor; TNFR, tumor necrosis factor receptor; TRADD, TNFR-associated death domain. Gastroenterology 2001 120, 294-298DOI: (10.1053/gast.2001.21402) Copyright © 2001 American Gastroenterological Association Terms and Conditions