A urokinase receptor-associated protein with specific collagen binding properties
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A urokinase receptor-associated protein with specific collagen binding properties. / Behrendt, N; Jensen, O N; Engelholm, L H; Mørtz, E; Mann, M; Danø, K.
I: The Journal of Biological Chemistry, Bind 275, Nr. 3, 2000, s. 1993-2002.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A urokinase receptor-associated protein with specific collagen binding properties
AU - Behrendt, N
AU - Jensen, O N
AU - Engelholm, L H
AU - Mørtz, E
AU - Mann, M
AU - Danø, K
PY - 2000
Y1 - 2000
N2 - The plasminogen activation cascade system, directed by urokinase and the urokinase receptor, plays a key role in extracellular proteolysis during tissue remodeling. To identify molecular interaction partners of these trigger proteins on the cell, we combined covalent protein cross-linking with mass spectrometry based methods for peptide mapping and primary structure analysis of electrophoretically isolated protein conjugates. A specific tri-molecular complex was observed upon addition of pro-urokinase to human U937 cells. This complex included the urokinase receptor, pro-urokinase, and an unknown, high molecular weight urokinase receptor-associated protein. The tryptic peptide mixture derived from a cross-linked complex of pro-urokinase and the latter protein was analyzed by nanoelectrospray tandem mass spectrometric sequencing. This analysis identified the novel protein as the human homologue of a murine membrane-bound lectin with hitherto unknown function. The human cDNA was cloned and sequenced. The protein, designated uPARAP, is a member of the macrophage mannose receptor protein family and contains a putative collagen-binding (fibronectin type II) domain in addition to 8 C-type carbohydrate recognition domains. It proved capable of binding strongly to a single type of collagen, collagen V. This collagen binding reaction at the exact site of plasminogen activation on the cell may lead to adhesive functions as well as a contribution to cellular degradation of collagen matrices.
AB - The plasminogen activation cascade system, directed by urokinase and the urokinase receptor, plays a key role in extracellular proteolysis during tissue remodeling. To identify molecular interaction partners of these trigger proteins on the cell, we combined covalent protein cross-linking with mass spectrometry based methods for peptide mapping and primary structure analysis of electrophoretically isolated protein conjugates. A specific tri-molecular complex was observed upon addition of pro-urokinase to human U937 cells. This complex included the urokinase receptor, pro-urokinase, and an unknown, high molecular weight urokinase receptor-associated protein. The tryptic peptide mixture derived from a cross-linked complex of pro-urokinase and the latter protein was analyzed by nanoelectrospray tandem mass spectrometric sequencing. This analysis identified the novel protein as the human homologue of a murine membrane-bound lectin with hitherto unknown function. The human cDNA was cloned and sequenced. The protein, designated uPARAP, is a member of the macrophage mannose receptor protein family and contains a putative collagen-binding (fibronectin type II) domain in addition to 8 C-type carbohydrate recognition domains. It proved capable of binding strongly to a single type of collagen, collagen V. This collagen binding reaction at the exact site of plasminogen activation on the cell may lead to adhesive functions as well as a contribution to cellular degradation of collagen matrices.
KW - Amino Acid Sequence
KW - Animals
KW - Cloning, Molecular
KW - Collagen
KW - Cross-Linking Reagents
KW - Dose-Response Relationship, Drug
KW - Glycosylation
KW - Humans
KW - Mannose-Binding Lectins
KW - Mass Spectrometry
KW - Membrane Glycoproteins
KW - Mice
KW - Molecular Sequence Data
KW - Muscle, Smooth, Vascular
KW - Plasminogen Activators
KW - Protein Binding
KW - Protein Structure, Tertiary
KW - Receptors, Cell Surface
KW - Receptors, Urokinase Plasminogen Activator
KW - Sequence Homology, Amino Acid
KW - U937 Cells
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - Journal article
C2 - 10636902
VL - 275
SP - 1993
EP - 2002
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 3
ER -
ID: 180823352