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Evidence implicating a mid‐region sequence of IGFBP‐3 in its specific IGF‐independent actions
Author(s) -
Hollowood A.D.,
Stewart C.E.H.,
Perks C.M.,
Pell J.M.,
Lai T.,
Alderson D.,
Holly J.M.P.
Publication year - 2002
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.10223
Subject(s) - serine , phosphorylation , biology , growth factor , binding protein , insulin like growth factor binding protein , insulin like growth factor , cell culture , cell growth , insulin , apoptosis , function (biology) , peptide , somatomedin , amino acid , microbiology and biotechnology , biochemistry , endocrinology , receptor , genetics , gene
Insulin‐like growth factor binding protein‐3 (IGFBP‐3) is one of six high affinity‐binding proteins that share a common function in regulating the bioavailability of the insulin‐like growth factors. The six binding proteins have highly conserved C‐ and N‐terminals that are essential to this function. Additionally, they all have specific functions on cellular homeostasis independent to the regulation of the insulin‐like growth factors. It has previously been shown that insulin‐like growth factor binding protein‐3 can accentuate UV‐induced apoptosis in a human carcinoma cell line. Using the KYSE 190 oesophageal carcinoma cell line we have demonstrated that a 15 amino acid (aa) peptide that lies within the mid‐region of the protein can mimic the effect of the intact protein. This region contains the serine residues Ser 111 and Ser 113 . Using two protocols, we modified these serine residues and have shown that both phosphorylation and derivatization of IGFBP‐3 can negate the accentuation of UV‐induced cell death. These three independent pieces of evidence support the hypothesis that the variable mid‐region is responsible for the specific pro‐apoptotic functions of IGFBP‐3, and suggest that phosphorylation may provide a mechanism for regulation of this action. J. Cell. Biochem. 86: 583–589, 2002. © 2002 Wiley‐Liss, Inc.