2007
DOI: 10.1016/j.intimp.2007.07.014
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Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator

Abstract: Human carboxypeptidase N (CPN) was discovered in the early 1960s as a plasma enzyme that inactivates bradykinin and was identified 8 years later as the major "anaphylatoxin inactivator" of blood. CPN plays in important role in protecting the body from excessive buildup of potentially deleterious peptides that normally act as local autocrine or paracrine hormones. This review summarizes the structure, enzymatic properties and function of this important human enzyme, including insights gained by the recent eluci… Show more

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Cited by 57 publications
(51 citation statements)
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“…Because these kinins are the peptides released from the precursor kininogen, they require further processing to generate B1R agonists. The assembly of CPM and B1R into a functional protein complex can thus facilitate B1R signaling by generating B1R agonist in close proximity to the receptor and is concordant with the current views that B1R signaling requires generation of DABK and DAKD (12,58). However, this study shows that the CPM⅐B1R protein complex provides an additional novel pathway for initiation of B1R-mediated kinin signaling that is dependent on substrate binding to CPM but independent of kinin cleavage (Fig.…”
Section: Discussionsupporting
confidence: 89%
“…Because these kinins are the peptides released from the precursor kininogen, they require further processing to generate B1R agonists. The assembly of CPM and B1R into a functional protein complex can thus facilitate B1R signaling by generating B1R agonist in close proximity to the receptor and is concordant with the current views that B1R signaling requires generation of DABK and DAKD (12,58). However, this study shows that the CPM⅐B1R protein complex provides an additional novel pathway for initiation of B1R-mediated kinin signaling that is dependent on substrate binding to CPM but independent of kinin cleavage (Fig.…”
Section: Discussionsupporting
confidence: 89%
“…[15][16][17] We identified and quantified 562 proteins of which 74 were increased at least 2-fold in patients with GVHD (supplemental Table 5). Five proteins (carboxypeptidase N catalytic chain precursor, pancreatic secretory trypsin inhibitor precursor, palladin, lithostathine 1-␣ precursor, and regenerating islet-derived 3-alpha) were preferentially expressed in the GI tract based on the relevant literature [21][22][23][24][25] and the Human Protein Atlas (http://www.proteinatlas. org/).…”
Section: Discovery Studymentioning
confidence: 99%
“…NRM was twice as high in patients with high REG3␣ concentrations, and this difference remained significant after adjusting for known risk factors of donor type, degree of HLA match, conditioning intensity, age, and baseline disease severity (59% [95% confidence interval [CI], 48%-69%] vs 34%[95% CI, 24%-46%], P Ͻ .001, Figure 4B). The incidence of relapse mortality was comparable for both groups (14% [95% CI, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] vs 17% [95% CI, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24], P ϭ .5; Figure 4C), and thus patients with high REG3␣ concentrations at the time of GVHD diagnosis experienced significantly inferior 1-year OS (27% [95% CI, 19%-39%] vs 48% [95% CI, 38%-61%], P ϭ .001; Figure 4D). …”
Section: Prognostic Value Of Reg3␣ Concentrations In Patients With Lomentioning
confidence: 99%
“…13). CPN is a tetramer composed of two large subunits, designated CPN2 (83 M r each), and two small subunits, designated CPN1 (52 M r each).…”
mentioning
confidence: 99%