The C-terminal 26-residue peptide of serpin A1 stimulates proliferation of breast and liver cancer cells: role of protein kinase C and CD47

• Published in: FEBS letters 2004-10, Vol.576 (3), p.343-347
• Main Authors: Congote, Luis Fernando, Temmel, Nyssa
• Format: Article
• Language: English
• Subjects: 4N1-1, RFYVVMWK; alpha 1-Antitrypsin - chemistry; alpha 1-Antitrypsin - pharmacology; Amino Acid Sequence; Antigens, CD - genetics; Antigens, CD - physiology; Breast Neoplasms - pathology; C26, PFVFLMIEQNTKSPLFMGKVVNPTQK; C26p, C26 phosphorylated at T24; C26t, PFVFLMIEQNTKSPLFMGRVVMPTQK; Carcinoma, Hepatocellular - pathology; CD36; CD47 Antigen; Cell Division - drug effects; Cell Line, Tumor; EGF, epidermal growth factor; Enzyme Inhibitors - pharmacology; Epidermal growth factor; GAPDH, glycerylaldehyde-3-phosphate dehydrogenase; Humans; Integrin-associated protein; Liver Neoplasms - pathology; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Phosphorylation; PKC, protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; RNA, Small Interfering - genetics; siRNA, short interfering RNA; α1-Antitrypsin; β1-Integrin
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.09.035

C26, the C-terminal 26 residue peptide of serpin A1, significantly increased cell proliferation in cultures of hepatoma cells, but not in porcine kidney epithelial cells, human skin fibroblasts or keratinocytes. The mitogenic activity of C26 was preferentially inhibited with a protein kinase C (PKC) inhibitor, an antibody against CD47 and CD47 short interfering RNA. The mutant C26-K19R,N22M, imitating a thrombospondin-like cell adhesion motif, increased the mitogenic activity in both Hep G2 cells and MCF-7 breast cancer cells. Phosphorylation of C26 at T24 (a putative PKC phosphorylation site) resulted in a 1.9–2.5 increase in mitogenic activity over C26 in MCF-7 cells.