title: RGD peptides released from beta ig-h3, a TGF-beta-induced cell-adhesive molecule, mediate apoptosis.
abstract: Beta ig-h3 is a transforming growth factor-beta (TGF-beta)-induced cell-adhesive molecule and has an RGD sequence at its C-terminus. A previous report suggested that beta ig-h3 normally undergoes carboxy-terminal processing that results in the loss of the RGD sequence. RGD peptides appear to play various roles in cell function. Here we show that the RGD peptides released from beta ig-h3 may facilitate TGF-beta-induced apoptosis. We found that carboxy-terminal cleavage of beta ig-h3 occurred after its secretion, and that overexpression of the wild-type beta ig-h3 induced apoptosis, unlike the C-terminal deleted but RGD-containing mutant beta ig-h3, which is resistant to C-terminal processing. The beta ig-h3-induced apoptosis was abolished by either deletion of the RGD sequence or mutation of RGD to RAE. Synthetic peptides of ERGDEL and GRGDSP derived from beta ig-h3 and fibronectin, respectively, also induced apoptosis, unlike ERGEEL and GRGESP. Culture supernatants of cells overexpressing beta ig-h3 filtered to isolate molecules smaller than 3 kDa also induced apoptosis. A fusion protein composed of the N-terminal 100 amino acids of fibronectin and the RGD-containing C-terminal part of beta ig-h3 was also subjected to C-terminal cleavage and overexpression resulted in apoptosis. The anti-beta ig-h3 antibody blocks TGF-beta-induced apoptosis. Thus, beta ig-h3 may be important in regulating cell apoptosis by providing soluble RGD peptides.
authors.affiliation: Department of Biochemistry, Kyungpook National University School of Medicine, Taegu, Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Song-Ja
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ha-Won
authors.initials: HW
authors.lastname: Jeong
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D016326:Extracellular Matrix Proteins; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D008985:Monensin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000502:physiology; D017384:Sequence Deletion; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D000099222:betaIG-H3 Protein
chemical_list: D000911:Antibodies, Monoclonal; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D008985:Monensin; D009363:Neoplasm Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C047981:arginyl-glycyl-aspartic acid; C058347:glycyl-arginyl-glycyl-glutamyl-seryl-proline