Regulation of EGF receptor signaling by the MARVEL domain-containing protein CKLFSF8.

Abstract:

:It is known that chemokine-like factor superfamily 8 (CKLFSF8), a member of the CKLF superfamily, has four putative transmembrane regions and a MARVEL domain. Its structure is similar to TM4SF11 (plasmolipin) and widely distributed in normal tissue. However, its function is not yet known. We show here that CKLFSF8 is associated with the epidermal growth factor receptor (EGFR) and that ectopic expression of CKLFSF8 in several cell lines suppresses EGF-induced cell proliferation, whereas knockdown of CKLFSF8 by siRNA promotes cell proliferation. In cells overexpressing CKLFSF8, the initial activation of EGFR was not affected, but subsequent desensitization of EGF-induced signaling occurred rapidly. This attenuation was correlated with an increased rate of receptor endocytosis. In contrast, knockdown of CKLFSF8 by siCKLFSF8 delayed EGFR endocytosis. These results identify CKLFSF8 as a novel regulator of EGF-induced signaling and indicate that the association of EGFR with four transmembrane proteins is critical for EGFR desensitization.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Jin C,Ding P,Wang Y,Ma D

doi

10.1016/j.febslet.2005.10.021

keywords:

subject

Has Abstract

pub_date

2005-11-21 00:00:00

pages

6375-82

issue

28

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(05)01268-8

journal_volume

579

pub_type

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