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. 1994 May 15;13(10):2322–2330. doi: 10.1002/j.1460-2075.1994.tb06516.x

Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity.

R Iwamoto 1, S Higashiyama 1, T Mitamura 1, N Taniguchi 1, M Klagsbrun 1, E Mekada 1
PMCID: PMC395097  PMID: 8194524

Abstract

DRAP27, the monkey homolog of human CD9 antigen (DRAP27/CD9) and diphtheria toxin receptor (DTR) were expressed in mouse L cells. L cells transfected transiently with both DRAP27/CD9 and DTR cDNA bound approximately 10 times more diphtheria toxin (DT) than cells transfected with DTR alone. Stable L cell transfectants expressing both DTR and DRAP27/CD9 (LCH-1 cells) had 15 times more cell surface DT-binding sites and were 20 times more sensitive to DT than were stable L cell transfectants expressing DTR alone (LH-1 cells). Increased DT-binding and DT sensitivity were not due to increased DTR transcription or increased cell surface DTR protein. Co-immunoprecipitation of DRAP27/CD9 with DTR and chemical cross-linking suggest a tight association of these membrane-bound proteins. In addition, the identity of DTR and a growth factor (HB-EGF) was established. Immobilized DT specifically adsorbed HB-EGF precursor solubilized from transfected L cells and [125I]DT bound to immobilized recombinant HB-EGF. We conclude that DRAP27/CD9 associates tightly with DTR/HB-EGF and up-regulates the number of functional DTRs and DT sensitivity, and that HB-EGF is identical to DTR.

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