Possible role of coexpression of CD9 with membrane-anchored heparin-binding EGF-like growth factor and amphiregulin in cultured human keratinocyte growth.
CD9 is a protein with 4 transmembrane domains, and functions as a cell surface antigen. We have previously reported that CD9 functions as an up-regulator of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) activity, which is a potent mitogen as well as a soluble HB-EGF. Anti-CD9 antibodies can neutralize the juxtacrine activity of proHB-EGF when both CD9 and proHB-EGF are coexpressed. We demonstrated here: (1) the CD9 gene was transcribed and translated in the cultured human keratinocytes; (2) anti-CD9 antibody inhibited the approximately 50% growth of human keratinocytes in culture; (3) CD9 was coprecipitated with proHB-EGF and membrane-anchored amphiregulin (proAR), and (4) the transient coexpression of CD9 with proHB-EGF or proAR in mouse L cells up-regulated their juxtacrine growth factor activities. These results suggest that CD9 would make a heterodimer and/or trimer complex with proHB-EGF and proAR, and might cooperate with proHB-EGF and proAR for human keratinocyte growth in a juxtacrine manner.
Inui
S
S
Department of Biochemistry, Osaka University Medical School, Japan.
Higashiyama
S
S
Hashimoto
K
K
Higashiyama
M
M
Yoshikawa
K
K
Taniguchi
N
N
D066258:Amphiregulin; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins; D051379:Mice; D011940:Receptor Aggregation; D060245:Tetraspanin 29
C587848:AREG protein, human; D066258:Amphiregulin; D015703:Antigens, CD; C587849:Areg protein, mouse; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D004815:Epidermal Growth Factor