M6P/IGFII-receptor complexes urokinase receptor and plasminogen for activation of transforming growth factor-beta1.
Transforming growth factor-beta1 (TGF-beta1) is a critical cytokine for cell proliferation and differentiation. It is secreted by many cells in a latent pro-form (LTGF-beta1) from which biologically active TGF-beta1 is released by an in vivo mechanism that is not known. Here we show that the mannose-6-phosphate/insulin-like growth factor II-receptor (M6P/IGFII-R), which binds LTGF-beta1, complexes with urokinase (plasminogen activator)-receptor (uPA-R) on the surface of human monocytes and directly binds plasminogen (Plg). Plasmin generated from Plg in the complex mediates release of TGF-beta1 when M6P/IGFII-R is associated with uPA-R. Thus, this interaction of M6P/IGFII-R and uPA-R suggests a potential mechanism for the generation of TGF-beta1 by cells.
Godár
S
S
Institute of Immunology, Vienna International Research Cooperation Center at NFI, University of Vienna, Austria.
Horejsi
V
V
Weidle
U H
UH
Binder
B R
BR
Hansmann
C
C
Stockinger
H
H
D000595:Amino Acid Sequence; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C524898:PLAUR protein, human; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta; D010958:Plasminogen; D005341:Fibrinolysin