Midkine stimulates Wilms' tumor cell proliferation via its signaling receptor.
Midkine, but not pleiotrophin, is mitogenic to human Wilms' tumor cells (G401 line) in dose-dependent and time-dependent fashion. Midkine specifically binds to high affinity (Kd = 0.15 +/- 0.02 nM, 210 kDa) and low affinity receptors (Kd = 0.65 +/- 0.07 nM, 75 kDa) on G401 cell surface, that has been confirmed by cross-linking and competition experiments. In addition, midkine stimulates a tyrosine phosphorylation of several proteins with molecular weight about 110-115 kDa, 130-140 kDa and 210 kDa. These data allow us to suggest that a key point in stimulation of G401 cell proliferation is interaction of midkine to its signaling receptor.
Ratovitski
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EA
Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21287-6417, USA.
Burrow
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CR
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism; D007700:Kinetics; D000078792:Midkine; D008934:Mitogens / Q000494:pharmacology*; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D009396:Wilms Tumor / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D017931:DNA Primers; D008934:Mitogens; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; C066845:pleiotrophin; D000078792:Midkine; D014443:Tyrosine