2 CARBOXYLESTERASES BIND C-REACTIVE PROTEIN WITHIN THE ENDOPLASMIC-RETICULUM AND REGULATE ITS SECRETION DURING THE ACUTE-PHASE RESPONSE

Citation
S. Macintyre et al., 2 CARBOXYLESTERASES BIND C-REACTIVE PROTEIN WITHIN THE ENDOPLASMIC-RETICULUM AND REGULATE ITS SECRETION DURING THE ACUTE-PHASE RESPONSE, The Journal of biological chemistry, 269(39), 1994, pp. 24496-24503
Citations number
52
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
269
Issue
39
Year of publication
1994
Pages
24496 - 24503
Database
ISI
SICI code
0021-9258(1994)269:39<24496:2CBCPW>2.0.ZU;2-D
Abstract
We have previously reported that C-reactive protein (CRP) is normally synthesized by rabbit hepatocytes at relatively low rates and is retai ned in the endoplasmic reticulum (ER), apparently by specific interact ion with a 60-kDa lumenal ER protein. During the acute phase response to tissue injury, a marked increase in CRP synthesis is associated wit h a decrease in the CRP binding capacity of the 60-kDa protein, with a ccompanying rapid secretion of CRP. In the present studies, we purifie d two 60-kDa ER lumenal glycoproteins (referred to as gp60a and gp60b) capable of binding CRP. gp60b, though present at only 5% the level of gp60a, was found to account for 80% of the total CRP binding capacity . Amino-terminal amino acid sequence analysis and biochemical characte rization identified gp60a and gp60b as two microsomal carboxylesterase s previously reported by others to contain COOH-terminal ER retention signals (HIEL and HTEL). The CRP binding activities of gp60a and gp60b were found to be independent of their esterase activities. In animals undergoing the acute phase response, the levels of gp60a and gp60b we re diminished by about 50%, but the CRP binding capacities were reduce d by 4-6-fold for gp60a and 25-30-fold for gp60b. These findings indic ate that CRP is normally retained within the ER via interaction with g p60a and gp60b, while during the acute phase response a decrease in th e CRP binding affinity of these proteins, particularly gp60b, results in efficient secretion of CRP.