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The RGD integrin binding site in human L1-CAM is important for nuclear signaling.

Abstract：

:L1 cell adhesion molecule (L1-CAM) is a transmembrane cell adhesion molecule initially defined as a promigratory molecule in the developing nervous system. L1 is also overexpressed in a variety of human carcinomas and is associated with bad prognosis. In carcinoma cell lines L1 augments cell motility and metastasis, tumor growth in nude mice and induces expression of L1-dependent genes. It is not known whether L1-signaling requires ligand binding. The RGD motif in the sixth Ig domain of L1 is a binding site for integrins. In the present study we analyzed the role of RGDs in L1-signaling using site-directed mutagenesis combined with antibody blocking studies. We observed that L1-RGE expressing HEK293 cells showed reduced cell-cell binding, cell motility, invasiveness and tumor growth in NOD/SCID mice. The RGE-mutation impaired L1-dependent gene regulation and antibodies to alphavbeta5 integrin had similar effects. Mutant L1 was unable to translocate to the nucleus. Our findings highlight the importance of the RGD site in L1 for human tumors and suggest that nuclear signaling of L1 is dependent on integrins.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Gast D,Riedle S,Kiefel H,Müerköster SS,Schäfer H,Schäfer MK,Altevogt P

doi

10.1016/j.yexcr.2008.04.004

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

2411-8

issue

13

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(08)00159-6

journal_volume

314

pub_type

杂志文章

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