Abstract
Originalsprog | Engelsk |
---|---|
Tidsskrift | Biochemical Journal |
Vol/bind | 356 |
Udgave nummer | Pt 2 |
Sider (fra-til) | 531-7 |
Antal sider | 6 |
ISSN | 0264-6021 |
Status | Udgivet - 2001 |
Bibliografisk note
Keywords: Amino Acid Sequence; Animals; Binding Sites; Caspase 3; Caspases; Cell Survival; Cells, Cultured; Embryo, Mammalian; Fibroblasts; Fibronectins; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Heparin; Integrins; Protein Structure, Tertiary; Protein-Tyrosine Kinases; Rats; Signal TransductionCitationsformater
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Rat embryo fibroblasts require both the cell-binding and the heparin-binding domains of fibronectin for survival. / Jeong, J; Han, I; Lim, Y; Kim, J; Park, I; Woods, A; Couchman, J R; Oh, E S.
I: Biochemical Journal, Bind 356, Nr. Pt 2, 2001, s. 531-7.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Rat embryo fibroblasts require both the cell-binding and the heparin-binding domains of fibronectin for survival.
AU - Jeong, J
AU - Han, I
AU - Lim, Y
AU - Kim, J
AU - Park, I
AU - Woods, A
AU - Couchman, J R
AU - Oh, E S
N1 - Keywords: Amino Acid Sequence; Animals; Binding Sites; Caspase 3; Caspases; Cell Survival; Cells, Cultured; Embryo, Mammalian; Fibroblasts; Fibronectins; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Heparin; Integrins; Protein Structure, Tertiary; Protein-Tyrosine Kinases; Rats; Signal Transduction
PY - 2001
Y1 - 2001
N2 - Fibronectin (FN) is known to transduce signal(s) to rescue cells from detachment-induced apoptosis (anoikis) through an integrin-mediated survival pathway. However, the functions of individual FN domains have not been studied in detail. In the present study we investigated whether the interaction of the cell-binding domain of FN with integrin is sufficient to rescue rat embryo fibroblasts (REFs) from detachment-induced apoptosis. REFs attached and spread normally after plating on substrates coated with either intact FN or a FN fragment, FN120, that contains the cell-binding domain but lacks the C-terminal heparin-binding domain, HepII. REFs on FN maintained a well-spread fibroblastic shape and even proliferated in serum-free medium at 20 h after plating. In contrast, previously well-spread REFs on FN120 started losing fibroblastic shape with time and detached from FN120-coated plates after approx. 8 h. Nuclear condensation indicated apototic cell death. This was due to the decreased activity/stability of focal adhesion kinase (pp125FAK) in the absence of HepII domain. A peptide in the HepII domain [peptide V, WQPPRARI (single-letter amino acid codes)], which has previously been implicated in cytoskeletal organization, rescued apoptotic changes. Consistently, pp125FAK phosphorylation was increased, and both cleavage of pp125FAK and activation of caspase 3 on FN120 were partly blocked by peptide V. Thus the interaction of the cell-binding domain with integrin has a major role in cell survival but is itself not sufficient for cell survival. One or more additional survival signals come from the HepII domain to regulate pp125FAK activity/stability.
AB - Fibronectin (FN) is known to transduce signal(s) to rescue cells from detachment-induced apoptosis (anoikis) through an integrin-mediated survival pathway. However, the functions of individual FN domains have not been studied in detail. In the present study we investigated whether the interaction of the cell-binding domain of FN with integrin is sufficient to rescue rat embryo fibroblasts (REFs) from detachment-induced apoptosis. REFs attached and spread normally after plating on substrates coated with either intact FN or a FN fragment, FN120, that contains the cell-binding domain but lacks the C-terminal heparin-binding domain, HepII. REFs on FN maintained a well-spread fibroblastic shape and even proliferated in serum-free medium at 20 h after plating. In contrast, previously well-spread REFs on FN120 started losing fibroblastic shape with time and detached from FN120-coated plates after approx. 8 h. Nuclear condensation indicated apototic cell death. This was due to the decreased activity/stability of focal adhesion kinase (pp125FAK) in the absence of HepII domain. A peptide in the HepII domain [peptide V, WQPPRARI (single-letter amino acid codes)], which has previously been implicated in cytoskeletal organization, rescued apoptotic changes. Consistently, pp125FAK phosphorylation was increased, and both cleavage of pp125FAK and activation of caspase 3 on FN120 were partly blocked by peptide V. Thus the interaction of the cell-binding domain with integrin has a major role in cell survival but is itself not sufficient for cell survival. One or more additional survival signals come from the HepII domain to regulate pp125FAK activity/stability.
M3 - Journal article
C2 - 11368782
VL - 356
SP - 531
EP - 537
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - Pt 2
ER -