Fitzgerald Trait

Saito, Hidehiko; Ratnoff, Oscar D.; Waldmann, Robert; Abraham, Joseph

doi:10.1172/jci108009

Cited by 199 publications

(29 citation statements)

References 20 publications

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“…Deficiency of Ferritin Binding Activity in H-kininogen-deficient Plasma-Kininogen deficiency is a rare genetic trait (26,27). The existence of kininogen deficiency syndromes allowed us to test whether ferritin binding activity and H-kininogen were genetically as well as biochemically related: if ferritin binding activity is attributable to human H-kininogen, we would predict that it should not be detectable in plasma obtained from H-kininogen-deficient individuals.…”

Section: Identification Of Ferritin-binding Proteins By Ligandmentioning

confidence: 99%

Human H-kininogen Is a Ferritin-binding Protein

Torti

1998

Journal of Biological Chemistry

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H-kininogen is a multifunctional protein: it inhibits cysteine proteases, plays a role in contact activation of the coagulation cascade, and is the precursor of the potent proinflammatory peptide bradykinin. In the experiments described here, we identify H-kininogen as a ferritin-binding protein. Ferritin is a cellular and serum protein that is elevated in acute and chronic inflammation and many cancers. Despite numerous reports of ferritin-binding protein(s) in human serum, the nature and function of these proteins remain unclear. As a first step in characterizing the interaction between ferritin and its binding protein(s), we devised a ligand blot assay and used it to guide purification of a ferritin-binding protein from human serum. Edman degradation of the purified protein determined the sequence HNLGHGH-K(H)ERDQGHG, a sequence with identity to residues 421-436 of human H-kininogen. These results were confirmed by demonstrating that commercially purified Hkininogen possessed ferritin binding activity and that ferritin binding could not be detected in plasma from kininogen-deficient individuals. Ligand blot assays mapped the ferritin binding domain to the light chain of H-kininogen chain, and revealed that both H and L recombinant ferritins possess H-kininogen binding activity. The unexpected identification of H-kininogen as a ferritin-binding protein may link ferritin in the complex chain of interactions by which H-kininogen mediates its multiple effects in contact activation and inflammation.

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Section: Identification Of Ferritin-binding Proteins By Ligandmentioning

confidence: 99%

Human H-kininogen Is a Ferritin-binding Protein

Torti

1998

Journal of Biological Chemistry

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“…Human plasma contains two distinct forms of kininogen with M, 120,000 (1)(2)(3)(4)(5) and 50,000-80,000 (6)(7)(8)(9), designated high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK), respectively. HMWK, together with either plasma prekallikrein or factor XI, is an important component in contact activation of the Hageman factor-dependent pathways (10)(11)(12)(13) and, in contrast to LMWK (6,8), serves as a substrate for both tissue and plasma kallikreins.…”

mentioning

confidence: 99%

Kinetic analysis of the interaction of human tissue kallikrein with single-chain human high and low molecular weight kininogens.

Maier¹,

Austen²,

Spragg³

1983

Proc. Natl. Acad. Sci. U.S.A.

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Human low molecular weight kininogen (LMWK) and high molecular weight kininogen (HMWK) have been purified to apparent homogeneity as intact, single-chain molecules. When they interacted with homologous urinary kallikrein, 0.9 mol of kinin per mol of substrate was released from LMWK and 0.7 mol of kinin per mol of substrate was released from HMWK. These functionally and structurally intact substrates have been used to obtain the kinetic constants for kinin release by purified human tissue kallikreins. With human urinary kallikrein, -apparent sec- (3,5,(15)(16)(17). Antibody specific for the human HMWK NH2-terminal chain recognizes both HMWK and LMWK, whereas antibody specific for the HMWK COOH-terminal chain recognizes only HMWK (18). Furthermore, the COOH-terminal chains of both bovine and human HMWK exhibit all the procoagulant activity of the intact molecule (2,19,20) whereas human and bovine LMWK lack this activity (10, 20), suggesting that the features that distinguish bovine HMWK and LMWK are also characteristics of human HMWK and LMWK. Glandular (tissue) kallikreins, which are found in kidney, pancreas, and salivary glands and in their secretions, are structurally, functionally, and antigenically different from plasma kallikrein but are related to each other (21-25). Glandular kallikrein has also been identified antigenically in human (26) and rat (27, 28) plasma, and the glandular kallikrein extracted from human plasma by a procedure that included immunoaffinity chromatography cleaved both synthetic substrates and HMWK (29). A single report (30) of the interaction of a glandular kallikrein-human salivary kallikrein-with human kininogen described the time-dependent cleavage of HMWK but did not present a detailed kinetic analysis or describe cleavage of LMWK.The difficulty in purifying LMWK as a fully active molecule free of albumin (31), some a-globulins of similar size and charge (32), and plasminogen (33, 34) has precluded adequate kinetic studies of human LMWK-enzyme interactions. Hence, the previous studies with human LMWK have used partially purified kininogen isolated under denaturing conditions (33,34). Purification of human LMWK to apparent homogeneity by a reproducible six-step procedure (9) and the availability of apparently homogeneous human HMWK (5) and tissue kallikreins (35-37) now permit the comparative kinetic analyses of kininogen cleavage by these enzymes. MATERIALS AND METHODSReagents. Sources were as follows: human albumin (purest), Behringwerke AG (Marburg, Federal Republic of Germany);Abbreviations: HMWK, high molecular weight kininogen; LMWK, low molecular weight kininogen; TAMe, a-N-p-tosyl-L-arginine methyl ester; LBTI, lima bean trypsin inhibitor; iPr2P-F, diisopropylfluorophosphate; BK, bradykinin; HUK, human urinary kallikrein; HPK, human pancreatic kallikrein.

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“…Proteins that are known to be involved in contact activation of human plasma include Hageman factor (HF, blood coagulation Factor XII) (6), plasma prekallikrein (Fletcher factor) (7,8), coagulation Factor XI (plasma thromboplastin antecedent) (9), and high molecular weight (Mr) kininogen, which was recognized in studies.of Flaujeac trait (10), Fitzgerald trait (11,12), Williams trait (13), and "contact activation cofactor" (14).…”

mentioning

confidence: 99%

Role of surface in surface-dependent activation of Hageman factor (blood coagulation Factor XII)

Griffin

1978

Proc. Natl. Acad. Sci. U.S.A.

245

143

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The mechanism by which negatively charged substances such as celite, kaolin, or ellagic acid contribute to the surface-dependent activation of Hageman factor (Factor XII) was studied. Kinetic studies of the proteolytic activation of '514-labeled human Hageman factor by human plasma kallikrein, plasmin, activated Factor XI, and trypsin were performed in the presence and absence of hig molecular, weight kininogen and surface materials such as celite, kaolin, or ellagic acid. The results showed that surface-bound Hageman factor was 500 times more susceptible than soluble Hageman factor to proteolytic activation by kallikrein in the presence of high molecular weight kininogen. Surface binding of Hageman factor enhanced its cleavage by plasmin, activated Factor XI, and trypsin by 100-fold, 30-fold, and 5-fold, respectively. On a molar basis, trypsin was twice as potent as kallikrein in the cleavage of the surface-bound Hageman factor, while plasmin and activated Factor XI were an order of magnitude less potent than kallikrein. Kallikrein even at concentrations as low as 0.5 nM (i.e., 1/1000th of the concentration of prekallikrein' in plasma) was very potent in the limited proteolysis of the surface-boulid Hageman factor. These results suggest that substances classically known as "activating surfaces" promote the activation of Hageman factor indirectly by alerng its structure such that it is much more susceptible to proteolytic activation by otherplasma or cellular proteases.

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Fitzgerald Trait

Cited by 199 publications

References 20 publications

Human H-kininogen Is a Ferritin-binding Protein

Human H-kininogen Is a Ferritin-binding Protein

Kinetic analysis of the interaction of human tissue kallikrein with single-chain human high and low molecular weight kininogens.

Role of surface in surface-dependent activation of Hageman factor (blood coagulation Factor XII)

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