The effect of ϵ-amino caproic acid on the gross conformation of plasminogen and plasmin

Violand, Bernard N.; Sodetz, James M.

doi:10.1016/0003-9861(75)90121-6

Cited by 85 publications

(50 citation statements)

References 18 publications

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“…Likewise, sequencing of spot 1 also yielded a peptide corresponding to amino acids 360 -372 of the ␤-and ␥-actin sequences and therefore is also consistent only with exposure of either K 373 or R 372 on the cell surface. The results are most consistent with cell-surface exposure of K 373 (with the structure of EACA) because EACA interacts with plaminogen with an affinity, in the range of the affinity of plasminogen for the cells (Violand et al, 1975;Markus et al, 1978;Parmer et al, 2000), whereas the affinity of arginine for plasminogen is ϳ10-fold lower (Violand et al, 1975).…”

Section: Identification Of Cpb-sensitive Cell-surface Plasminogen-binsupporting

confidence: 62%

“…This result suggests that the plasminogen receptors that are sensitive to CpB [i.e., proteins exposing C-terminal lysines (with the conformation of EACA) on the cell surface] are primarily responsible for the promotion of plasminogen activation by these cells. Although CpB also can remove C-terminal arginyl residues, the results are most consistent with an effect on a C-terminal lysyl residue because EACA interacts with plaminogen with an affinity in the range of the affinity of plasminogen for the cells (Violand et al, 1975;Markus et al, 1978;Parmer et al, 2000), whereas the affinity of arginine for plasminogen is ϳ10-fold lower (Violand et al, 1975).…”

Section: Role Of C-terminal Lysines In Plasminogen Binding and Activamentioning

confidence: 82%

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Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells

Miles¹,

Andronicos²,

Baik³

et al. 2006

J. Neurosci.

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An emerging area of research has documented a novel role for the plasminogen activation system in the regulation of neurotransmitter release. Prohormones, secreted by cells within the sympathoadrenal system, are processed by plasmin to bioactive peptides that feed back to inhibit secretagogue-stimulated release. Catecholaminergic cells of the sympathoadrenal system are prototypic prohormone-secreting cells. Processing of prohormones by plasmin is enhanced in the presence of catecholaminergic cells, and the enhancement requires binding of plasmin(ogen) to cellular receptors. Consequently, modulation of the local cellular fibrinolytic system of catecholaminergic cells results in substantial changes in catecholamine release. However, mechanisms for enhancing prohormone processing and cellsurface molecules mediating the enhancement on catecholaminergic cells have not been investigated. Here we show that plasminogen activation was enhanced Ͼ6.5-fold on catecholaminergic cells. Carboxypeptidase B treatment decreased cell-dependent plasminogen activation by ϳ90%, suggesting that the binding of plasminogen to proteins exposing C-terminal lysines on the cell surface is required to promote plasminogen activation. We identified catecholaminergic plasminogen receptors required for enhancing plasminogen activation, using a novel strategy combining targeted specific proteolysis using carboxypeptidase B with a proteomics approach using twodimensional gel electrophoresis, radioligand blotting, and tandem mass spectrometry. Two major plasminogen-binding proteins that exposed C-terminal lysines on the cell surface contained amino acid sequences corresponding to ␤/␥-actin. An anti-actin monoclonal antibody inhibited cell-dependent plasminogen activation and also enhanced nicotine-dependent catecholamine release. Our results suggest that cell-surface-expressed forms of actin bind plasminogen, thereby promoting plasminogen activation and increased prohormone processing leading to inhibition of neurotransmitter release.

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Section: Identification Of Cpb-sensitive Cell-surface Plasminogen-binsupporting

confidence: 62%

Section: Role Of C-terminal Lysines In Plasminogen Binding and Activamentioning

confidence: 82%

Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells

Miles¹,

Andronicos²,

Baik³

et al. 2006

J. Neurosci.

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“…Unexpectedly, all monomeric con- To discover the effects of monomeric and dimeric VEK-peptides on hPg conformation we also performed a real-time SAX analysis of hPg using VEK35 and VEK75. Full-length hPg can exist in a closed (T), poorly activatable conformation, and an open (R), highly activatable, conformation (33,34). The transition from the closed to the open conformation is induced by LBS binding effectors, such as EACA and its analogues (34).…”

Section: Resultsmentioning

confidence: 99%

Dimerization Is Not a Determining Factor for Functional High Affinity Human Plasminogen Binding by the Group A Streptococcal Virulence Factor PAM and Is Mediated by Specific Residues within the PAM a1a2 Domain

Bhattacharya

Zhong

Quek

et al. 2014

Journal of Biological Chemistry

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Background: High affinity human plasminogen (hPg) binding to Group A Streptococcus (GAS) is mediated by the coiledcoil M-like protein, PAM. Results: Amino acid residues in the a1a2 domain of PAM direct high affinity PAM/hPg binding regardless of oligomerization status of PAM. Conclusion: The a1a2 domain defines its hPg binding site, regardless of PAM dimerization. Significance: The virulence of GAS is altered by mutations in PAM(a1a2).

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“…Instead, the fibrin selectivity of pro-UK in plasma has been attributed to its selective activation of fibrin-bound plasminogen (5) due to the conformational change that occurs in Glu-plasminogen when its high affinity lysine binding site is occupied by a lysine residue (6). This conformational change makes it functionally equivalent to Lys-plasminogen, which is far more sensitive to activation by pro-UK than is Glu-plasminogen (7).…”

Section: Introductionmentioning

confidence: 99%

Complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained.

Pannell¹,

Black²,

Gurewich³

1988

J. Clin. Invest.

150

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Tissue plasminogen activator (t-PA) and/or pro-urokinase (pro-UK) induced lysis of standard '251-fibrin clots suspended in plasma was studied. Doses were kept below the concentration at which a nonspecific effect was seen, i.e., where fibrinogenolysis and major plasminogen consumption were observed. Small amounts of t-PA potentiated clot lysis by pro-UK by attenuating the lag phase characteristic of pro-UK, and causing a much earlier transition to the rapid phase of lysis. Similar promotion of the fibrinolytic effect of pro-UK was obtained when clots were pretreated with UK or with a little plasmin (< 1% clot lysis). Promotion by plasmin was nullified by a subsequent treatment of the clot with carboxypeptidase B, indicating that the plasmin effect was related to the exposure of carboxy terminal lysine residues on fibrin. These lysine termini, absent in undegraded fibrin, are known to be essential for the high affinity binding of plasminogen to fibrin. In contrast, clot lysis by t-PA was unaffected by plasmin pretreatment and little affected by carboxypeptidase B treatment of the fibrin substrate. Therefore, plasminogen bound to lysine termini on fibrin, although found to be essential for pro-UK, did not appear to serve as a substrate for t-PA.Selective activation of fibrin bound plasminogen has been attributed to the conformational change in Glu-plasminogen that occurs as a result of binding. The present findings suggest that this conformational change occurs when plasminogen is bound to a terminal lysine but not to an internal lysine. Plasminogen bound to the latter site on fibrin was activated by t-PA and therefore is involved in the ternary complex. This initiates lysis of the undegraded clot and exposes the plasminogen binding sites required by pro-UK. By their complementary activation of fibrin bound plasminogen, t-PA followed by pro-UK induces efficient and synergistic fibrinolysis, whereas each is relatively inefficient when used alone.

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The effect of ϵ-amino caproic acid on the gross conformation of plasminogen and plasmin

Cited by 85 publications

References 18 publications

Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells

Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells

Dimerization Is Not a Determining Factor for Functional High Affinity Human Plasminogen Binding by the Group A Streptococcal Virulence Factor PAM and Is Mediated by Specific Residues within the PAM a1a2 Domain

Complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained.

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