Regulation of EGF receptor signaling by the MARVEL domain-containing protein CKLFSF8.
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.
Jin
Caining
C
Lab of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, Peking University, No. 38 Xueyuan Road, Beijing 100083, China
Ding
Peiguo
P
Wang
Ying
Y
Ma
Dalong
D
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D062792:MARVEL Domain-Containing Proteins; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
C507076:CMTM8 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor; D066246:ErbB Receptors