MARY HEEB

Summary

Affiliation: The Scripps Research Institute
Country: USA

Publications

  1. pmc Plasma protein S residues 37-50 mediate its binding to factor Va and inhibition of blood coagulation
    Mary J Heeb
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 110:275-82. 2013
  2. pmc Phosphorylation of protein S by platelet kinases enhances its activated protein C cofactor activity
    Fabian Stavenuiter
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    FASEB J 27:2918-25. 2013
  3. pmc Platelet protein S directly inhibits procoagulant activity on platelets and microparticles
    Fabian Stavenuiter
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Thromb Haemost 109:229-37. 2013
  4. pmc Antithrombotic activity of protein S infused without activated protein C in a baboon thrombosis model
    M J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Thromb Haemost 107:690-8. 2012
  5. pmc Binding sites for blood coagulation factor Xa and protein S involving residues 493-506 in factor Va
    M J Heeb
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA
    Protein Sci 5:1883-9. 1996
  6. pmc Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor
    Mary J Heeb
    Department of Molecular and Experimental Medicine, MEM276, Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    FASEB J 23:2244-53. 2009
  7. ncbi request reprint Plasma contains protein S monomers and multimers with similar direct anticoagulant activity
    M J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 4:2215-22. 2006
  8. ncbi request reprint Protein S multimers and monomers each have direct anticoagulant activity
    M J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 4:385-91. 2006
  9. ncbi request reprint Down-regulation of factor IXa in the factor Xase complex by protein Z-dependent protease inhibitor
    Mary J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 280:33819-25. 2005
  10. ncbi request reprint Direct anticoagulant activity of protein S-C4b binding protein complex in Heerlen heterozygotes and normals
    M J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 2:1766-73. 2004

Research Grants

Detail Information

Publications22

  1. pmc Plasma protein S residues 37-50 mediate its binding to factor Va and inhibition of blood coagulation
    Mary J Heeb
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 110:275-82. 2013
    ..These data implicate PS residues 37-50 as a binding site for FVa that mediates, at least in part, the direct inhibition of FVa-dependent procoagulant activity by PS. ..
  2. pmc Phosphorylation of protein S by platelet kinases enhances its activated protein C cofactor activity
    Fabian Stavenuiter
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    FASEB J 27:2918-25. 2013
    ..Mass spectrometry revealed a phosphorylated CK2 site at Thr37 within the N-terminal Gla-domain. Thus, platelet-mediated extracellular phosphorylation of PS is a potential mechanism by which its activity is regulated...
  3. pmc Platelet protein S directly inhibits procoagulant activity on platelets and microparticles
    Fabian Stavenuiter
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Thromb Haemost 109:229-37. 2013
    ..Neutralising antibodies against APC and TFPI had no effect on the PS-direct of pltPS or pdPS on platelets. This study indicates that pltPS may be an essential pool of PS that counterbalances procoagulant activities on platelets...
  4. pmc Antithrombotic activity of protein S infused without activated protein C in a baboon thrombosis model
    M J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Thromb Haemost 107:690-8. 2012
    ..Thus, infused human Zn2+-containing ProS is antithrombotic in primates, and may have therapeutic potential even in protein C-deficient human patients...
  5. pmc Binding sites for blood coagulation factor Xa and protein S involving residues 493-506 in factor Va
    M J Heeb
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA
    Protein Sci 5:1883-9. 1996
    ..Possible loss of this FVa binding site for FXa due to cleavage at Arg 506 by APC may help explain why this cleavage causes 40% decrease in FVa activity and facilitates inactivation of FVa...
  6. pmc Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor
    Mary J Heeb
    Department of Molecular and Experimental Medicine, MEM276, Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    FASEB J 23:2244-53. 2009
    ..Thus, Zn(2+) is required for PS-direct and efficient FXa binding and may play a role in stabilizing PS conformation...
  7. ncbi request reprint Plasma contains protein S monomers and multimers with similar direct anticoagulant activity
    M J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 4:2215-22. 2006
    ..Protein S (PS) has activated protein C-independent, direct anticoagulant activity (PS-direct). We reported that both multimers and monomers of affinity-purified PS have PS-direct similar to that in plasma, in contrast to another report...
  8. ncbi request reprint Protein S multimers and monomers each have direct anticoagulant activity
    M J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 4:385-91. 2006
    ..We independently examined the relative PS-direct and affinity for phospholipids of monomeric and multimeric PS and we obtained contrasting results...
  9. ncbi request reprint Down-regulation of factor IXa in the factor Xase complex by protein Z-dependent protease inhibitor
    Mary J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 280:33819-25. 2005
    ..ZPI may be an unusual physiologic regulator of both the intrinsic FXase and the prothrombinase complexes...
  10. ncbi request reprint Direct anticoagulant activity of protein S-C4b binding protein complex in Heerlen heterozygotes and normals
    M J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 2:1766-73. 2004
    ..Protein S-Heerlen lacks a carbohydrate group, leading to low plasma free protein S levels, but normal levels of PS-C4BP...
  11. ncbi request reprint Activated protein C-dependent and -independent anticoagulant activities of protein S have different structural requirements
    Mary J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    Blood Cells Mol Dis 29:190-9. 2002
    ..Thus, the APC-cofactor activity protein S is significantly more sensitive to structural changes in the TSR than is the APC-independent activity of protein S...
  12. ncbi request reprint Low protein Z levels and risk of ischemic stroke: differences by diabetic status and gender
    Mary J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 29:139-44. 2002
    ..015). Protein Z is suggested to be a physiologic downregulator of blood coagulation and low protein Z levels are associated with increased risk of ischemic stroke, particularly in males and in the absence of diabetes...
  13. ncbi request reprint C-terminal residues 621-635 of protein S are essential for binding to factor Va
    M J Heeb
    Departments of Molecular and Experimental Medicine and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 274:36187-92. 1999
    ..These results show that the C-terminal region of protein S containing residues 621-635 is essential for binding of protein S to Factor Va and that this interaction contributes to anticoagulant action...
  14. ncbi request reprint Importance of individual activated protein C cleavage site regions in coagulation factor V for factor Va inactivation and for factor Xa activation
    M J Heeb
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
    Eur J Biochem 260:64-75. 1999
    ....
  15. ncbi request reprint alpha2-macroglobulin and C1-inactivator are plasma inhibitors of human glandular kallikrein
    M J Heeb
    Departments of Molecular and Experimental Medicine and of Vascular Biology, The Scripps Research Institute, La Jolla, CA
    Blood Cells Mol Dis 24:412-9. 1998
    ..Measurement of one or more of the hK2 forms identified here may have diagnostic or prognostic potential for prostate cancer...
  16. ncbi request reprint Binding of protein S to factor Va associated with inhibition of prothrombinase that is independent of activated protein C
    M J Heeb
    Committee on Vascular Biology, Scripps Research Institute, La Jolla, California 92037
    J Biol Chem 268:2872-7. 1993
    ..These data show that protein S has an anticoagulant function which is independent of activated protein C and, at least in part, that this is because of its competition with prothrombin for direct binding to Factor Va...
  17. pmc Protein S binds to and inhibits factor Xa
    M J Heeb
    Scripps Research Institute, La Jolla, CA 92037
    Proc Natl Acad Sci U S A 91:2728-32. 1994
    ..These data demonstrate mechanisms of anticoagulant action for protein S that are independent of activated protein C and that involve direct binding to factors Xa and Va and direct inhibition of factor Xa...
  18. ncbi request reprint Factor Va residues 311-325 represent an activated protein C binding region
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 282:28353-61. 2007
    ..These data suggest that peptide VP311-325 represents both an APC and fXa binding region in fVa...
  19. ncbi request reprint Gas6, a ligand for the receptor protein-tyrosine kinase Tyro-3, is widely expressed in the central nervous system
    A L Prieto
    Department of Neuropharmacology CVN12, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Brain Res 816:646-61. 1999
    ..The spatial and temporal profiles of Gas6 expression suggest that it could potentially serve as the physiologically relevant ligand for Tyro-3 in the postnatal rat nervous system...
  20. ncbi request reprint Association of low protein Z levels with ischemic stroke in young women
    Mary J Heeb
    Thromb Haemost 97:495-6. 2007
  21. ncbi request reprint Familial protein S deficiency with a variant protein S molecule in plasma and platelets
    H P Schwarz
    Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037
    Blood 74:213-21. 1989
    ....
  22. ncbi request reprint Both protein S and Gas6 stimulate outer segment phagocytosis by cultured rat retinal pigment epithelial cells
    Michael O Hall
    Jules Stein Eye Institute, UCLA Medical Center, 100 Stein Plaza, Los Angeles, CA 90095 7008, USA
    Exp Eye Res 81:581-91. 2005
    ..The existence of redundant ligands for Mer-dependent OS phagocytosis underscores the critical role of this process in the maintenance of retinal function...

Research Grants12

  1. New Aspects of Protein S Anticoagulant Activity
    MARY HEEB; Fiscal Year: 2009
    ..Insights may lead to new treatments, or measures that prevent thrombosis. ..
  2. Novel Anticoagulant Mechanisms
    MARY HEEB; Fiscal Year: 2006
    ..We will find whether a ZPI polymorphism we identified affects function. ..
  3. FORMS OF PROSTATE SPECIFIC ANTIGEN AND HK2 IN CANCER
    MARY HEEB; Fiscal Year: 2003
    ..Techniques will include protein purification, antibody and ELISA development, immunoblotting, enzyme activity assays, and peptide synthesis. ..
  4. New Aspects of Protein S Anticoagulant Activity
    Mary J Heeb; Fiscal Year: 2010
    ..Insights may lead to new treatments, or measures that prevent thrombosis. ..