In:
Journal of Cellular Biochemistry, Wiley, Vol. 89, No. 6 ( 2003-08-15), p. 1115-1125
Kurzfassung:
We have shown previously that the promotion of myofiber survival by the basement membrane component merosin (laminin‐2 [α2β1γ1]/laminin‐4 [α2β2γ1] ) is dependent on the activity of the tyrosine kinase Fyn, whereas myofiber anoikis induced by merosin deficiency is dependent on the stress‐activated protein kinase p38α. To further understand such merosin‐driven survival signaling, we analyzed the expression of five Bcl‐2 homologs (Bcl‐2, Bcl‐X L , Bax, Bak, Bad) and one non‐homologous associated molecule (Bag‐1) in normal and merosin‐deficient myotubes, with or without pharmacological inhibitors for Fyn and p38. Herein, we report that (1) merosin deficiency induces anoikis and causes decreased Bcl‐2, Bcl‐X L , and Bag‐1 levels, increased Bax and Bak levels, and decreased Bad phosphorylation; (2) Bcl‐2, Bcl‐X L , Bag‐1, and Bad phosphorylation are also decreased in anoikis‐dying, Fyn‐inhibited myotubes; (3) the inhibition of p38α in Fyn‐inhibited and/or merosin‐deficient myotubes protects against anoikis and increases Bcl‐2 levels above normal, in addition to restoring Bad phosphorylation and Bag‐1 levels to normal; (4) the overexpression of merosin in deficient myotubes also rescues from anoikis and increases Bcl‐2 levels and Bad phosphorylation above normal, in addition to restoring Bcl‐X L , Bag‐1, Bax, and Bak levels to normal; and (5) Bcl‐2 overexpression is sufficient to rescue merosin‐deficient myotubes from anoikis, even though the expression/phosphorylation levels of the other homologs analyzed are not restored to normal. These results indicate that merosin‐driven myofiber survival signaling affects complex, differential modulations of individual Bcl‐2 homologs. These further suggest that Bcl‐2 can play a major role in suppressing myofiber anoikis. © 2003 Wiley‐Liss, Inc.
Materialart:
Online-Ressource
ISSN:
0730-2312
,
1097-4644
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2003
ZDB Id:
1479976-5
SSG:
12
