Search tips
Search criteria 


Logo of molmedLink to Publisher's site
Mol Med. 1999 August; 5(8): 555–563.
PMCID: PMC2230456

Platelet glycoprotein Ib: a zinc-dependent binding protein for the heavy chain of high-molecular-weight kininogen.


Domains 3 and 5 of high-molecular-weight kininogen (HK) have been shown to bind to platelets in a zinc-dependent reaction. However, the platelet-binding proteins responsible for this interaction have not been identified. We have focused on the platelet-binding site for the heavy chain (domain 3), which we approached using a domain 3-derived peptide ligand and isolated binding proteins by affinity chromatography. The domain 3-derived peptide, thrombin, HK, factor XII, as well as antibody to glycocalicin (the N-terminal portion of the alpha chain of GPIb) recognized a protein at 74 kD. We also isolated the thrombin receptor (PAR 1) at 45 kD, however, none of the above-mentioned ligands bound to this protein. Isolation of platelet membrane proteins using a monoclonal anti-glycocalicin antibody column revealed the same HK binding protein at 74 kD, which was reactive with anti-GPIb and represents a GPIb fragment. By photoaffinity labeling, HK interacted with membrane GPIb, which was then isolated in native form (135 kD) along with gC1qR, a ligand for the HK light chain. Finally, (125)I-HK binding to platelets was significantly inhibited by the anti-GPIb antibody. These results suggest that the GPIb alpha chain, a known thrombin binding protein, is also one of the zinc-dependent platelet membrane binding sites for HK domain 3.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Greengard JS, Griffin JH. Receptors for high molecular weight kininogen on stimulated washed human platelets. Biochemistry. 1984 Dec 18;23(26):6863–6869. [PubMed]
  • Jiang YP, Muller-Esterl W, Schmaier AH. Domain 3 of kininogens contains a cell-binding site and a site that modifies thrombin activation of platelets. J Biol Chem. 1992 Feb 25;267(6):3712–3717. [PubMed]
  • Meloni FJ, Gustafson EJ, Schmaier AH. High molecular weight kininogen binds to platelets by its heavy and light chains and when bound has altered susceptibility to kallikrein cleavage. Blood. 1992 Mar 1;79(5):1233–1244. [PubMed]
  • Reddigari SR, Kuna P, Miragliotta G, Shibayama Y, Nishikawa K, Kaplan AP. Human high molecular weight kininogen binds to human umbilical vein endothelial cells via its heavy and light chains. Blood. 1993 Mar 1;81(5):1306–1311. [PubMed]
  • Hasan AA, Cines DB, Herwald H, Schmaier AH, Müller-Esterl W. Mapping the cell binding site on high molecular weight kininogen domain 5. J Biol Chem. 1995 Aug 18;270(33):19256–19261. [PubMed]
  • Herwald H, Hasan AA, Godovac-Zimmermann J, Schmaier AH, Müller-Esterl W. Identification of an endothelial cell binding site on kininogen domain D3. J Biol Chem. 1995 Jun 16;270(24):14634–14642. [PubMed]
  • Puri RN, Zhou F, Hu CJ, Colman RF, Colman RW. High molecular weight kininogen inhibits thrombin-induced platelet aggregation and cleavage of aggregin by inhibiting binding of thrombin to platelets. Blood. 1991 Feb 1;77(3):500–507. [PubMed]
  • Bradford HN, Dela Cadena RA, Kunapuli SP, Dong JF, Löpez JA, Colman RW. Human kininogens regulate thrombin binding to platelets through the glycoprotein Ib-IX-V complex. Blood. 1997 Aug 15;90(4):1508–1515. [PubMed]
  • Bahou WF, Coller BS, Potter CL, Norton KJ, Kutok JL, Goligorsky MS. The thrombin receptor extracellular domain contains sites crucial for peptide ligand-induced activation. J Clin Invest. 1993 Apr;91(4):1405–1413. [PMC free article] [PubMed]
  • Joseph K, Ghebrehiwet B, Peerschke EI, Reid KB, Kaplan AP. Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular "heads" of C1q (gC1q-R). Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8552–8557. [PubMed]
  • Nishikawa K, Shibayama Y, Kuna P, Calcaterra E, Kaplan AP, Reddigari SR. Generation of vasoactive peptide bradykinin from human umbilical vein endothelium-bound high molecular weight kininogen by plasma kallikrein. Blood. 1992 Oct 15;80(8):1980–1988. [PubMed]
  • PROCTOR RR, RAPAPORT SI. The partial thromboplastin time with kaolin. A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol. 1961 Sep;36:212–219. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. [PubMed]
  • Coller BS, Peerschke EI, Scudder LE, Sullivan CA. Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor. Blood. 1983 Jan;61(1):99–110. [PubMed]
  • Coller BS, Kalomiris E, Steinberg M, Scudder LE. Evidence that glycocalicin circulates in normal plasma. J Clin Invest. 1984 Mar;73(3):794–799. [PMC free article] [PubMed]
  • Wachtfogel YT, DeLa Cadena RA, Kunapuli SP, Rick L, Miller M, Schultze RL, Altieri DC, Edgington TS, Colman RW. High molecular weight kininogen binds to Mac-1 on neutrophils by its heavy chain (domain 3) and its light chain (domain 5). J Biol Chem. 1994 Jul 29;269(30):19307–19312. [PubMed]
  • Reddigari SR, Shibayama Y, Brunnée T, Kaplan AP. Human Hageman factor (factor XII) and high molecular weight kininogen compete for the same binding site on human umbilical vein endothelial cells. J Biol Chem. 1993 Jun 5;268(16):11982–11987. [PubMed]
  • Steinberg MH, Kelton JG, Coller BS. Plasma glycocalicin. An aid in the classification of thrombocytopenic disorders. N Engl J Med. 1987 Oct 22;317(17):1037–1042. [PubMed]
  • Vouret-Craviari V, Grall D, Chambard JC, Rasmussen UB, Pouysségur J, Van Obberghen-Schilling E. Post-translational and activation-dependent modifications of the G protein-coupled thrombin receptor. J Biol Chem. 1995 Apr 7;270(14):8367–8372. [PubMed]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ