Characterization of secretion defects of kininogens

• Published in: Japanese Journal of Pharmacology Vol. 73; no. suppl.1; p. 70
• Main Authors: Havashi, Izumi, Haaiwara, Yukari, Oh-ishi, Sachiko
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1997
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)44785-9

Kininogens are precursor glycoproteins of bioactive peptide, bradykinin. A secretion defct of high-molecular-weight kininogen (HK) by the liver of a mutant strain, Brown Norway (B/N-) Katholiek rat results in a severe deficiency of HK in its plasma. We found that this impared secretion was caused by an amino acid replacement of alanine [163] with threonine in the HK molecule. To characterize this secretion defect in detail, we examined intracellular localization of the mutant HK by immunofluorescent detection in the COS-1 cells tranfected with this mutant cDNA. The HK antigen was detected in not only endoplasmic reticulum but also Golgi compartment, indicating that this case is a different type of secretion defect from that reported in the case of defective α1-antitrypsin which was accumulated at endoplasmic reticulum. This result suggests the presence of a specific cellular sorting mechanism for unsecretable abnormal proteins to be recognized and degraded within cells even after proteins are transported into Golgi compartment.