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J. Biol. Chem., Vol. 278, Issue 16, 14533-14542, April 18, 2003
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From the Department of Molecular Cell Biology, The Weizmann
Institute of Science, Rehovot 76100, Israel
Galectin-8, a member of the galectin family of
mammalian lectins, is a secreted protein that promotes cell adhesion
and migration upon binding to a subset of integrins through
sugar-protein interactions. Ligation of integrins by galectin-8
triggers a distinct pattern of cytoskeletal organization, including
formation of F-actin-containing microspikes. This is associated with
activation of integrin-mediated signaling cascades (ERK and
phosphatidylinositol 3 kinase (PI3K)) that are much more robust and are
of longer duration than those induced upon cell adhesion to
fibronectin. Indeed, formation of microspikes is enhanced 40% in cells
that overexpress protein kinase B, the downstream effector of PI3K.
Inhibition of PI3K activity induced by wortmannin partially inhibits
cell adhesion and spreading while largely inhibiting microspike
formation in cells adherent to galectin-8. Furthermore, the inhibitory
effects of wortmannin are markedly accentuated in cells overexpressing PKB or p70S6K (CHOPKB and CHOp70S6K
cells), whose adhesion and spreading on galectin-8 (but not on fibronectin) is inhibited ~25-35% in the presence of wortmannin. The above results suggest that galectin-8 is an extracellular matrix protein that triggers a unique repertoire of integrin-mediated signals, which leads to a distinctive cytoskeletal organization and
microspike formation. They further suggest that downstream effectors of PI3K, including PKB and p70 S6 kinase, in part mediate cell adhesion, spreading, and microspike formation induced by galectin-8.
Sustained Induction of ERK, Protein Kinase B, and p70 S6 Kinase
Regulates Cell Spreading and Formation of F-actin Microspikes Upon
Ligation of Integrins by Galectin-8, a Mammalian Lectin*
*
This work was supported by grants from the CaPCure Israel
Foundation, the Moross Center for Cancer Research, and the Israel Cancer Association.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Incumbent of the Marte R. Gomez Professorial Chair. To whom
correspondence should be addressed. Tel.: 972-8-9342-380; Fax: 972-8-9344-125; E-mail: yehiel.zick@weizmann.ac.il.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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