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Signal peptide of eosinophil cationic protein upregulates transforming growth factor‐alpha expression in human cells
Author(s) -
Chang HaoTeng,
Kao YuLin,
Wu ChiaMao,
Fan Tanchi,
Lai YiuKay,
Huang KaiLing,
Chang YuoSheng,
Tsai JawJi,
Chang Margaret DahTsyr
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21120
Subject(s) - tgf alpha , autocrine signalling , eosinophil cationic protein , signal peptide , biology , microbiology and biotechnology , epidermal growth factor , transforming growth factor , pichia pastoris , downregulation and upregulation , peptide sequence , receptor , eosinophil , biochemistry , immunology , recombinant dna , gene , asthma
Eosinophil cationic protein (ECP) is a major component of eosinophil granule protein that is used as a clinical bio‐marker for asthma and allergic inflammatory diseases. Previously, it has been reported that the signal peptide of human ECP (ECPsp) inhibits the cell growth of Escherichia coli ( E. coli ) and Pichia pastoris ( P. pastoris ), but not mammalian A431 cells. The inhibitory effect is due to the lack of human signal peptide peptidase (hSPP), a protease located on the endoplasmic reticulum (ER) membrane, in the lower organisms. In this study, we show that the epidermal growth factor receptor (EGFR) is upregulated by the exogenous ECPsp‐eGFP as a result of the increased expression of the transforming growth factor‐alpha (TGF‐α) at both transcriptional and translational levels in A431 and HL‐60 clone 15 cell lines. Furthermore, the N‐terminus of ECPsp fragment generated by the cleavage of hSPP (ECPspM1‐G17) gives rise to over threefold increase of TGF‐α protein expression, whereas another ECPsp fragment (ECPspL18‐A27) and the hSPP‐resistant ECPsp (ECPspG17L) do not show similar effect. Our results indicate that the ECPspM1‐G17 plays a crucial role in the upregulation of TGF‐α, suggesting that the ECPsp not only directs the secretion of mature ECP, but also involves in the autocrine system. J. Cell. Biochem. 100: 1266–1275, 2007. © 2006 Wiley‐Liss, Inc.