Human kit ligand (stem cell factor) modulates platelet activation in vitro.
The human stem cell factor (SCF), also termed c-Kit ligand (KL), is a hematopoietic growth factor produced by mesenchymal cells that induces proliferation of bone marrow progenitor cells, megakaryocytes, and mast cells via interaction with c-Kit, its cognate receptor. Expression of the c-kit gene was identified in human platelets by the polymerase chain reaction technique. The presence of the c-Kit receptor was demonstrated by the specific binding of 125I-KL/SCF to ADP-stimulated platelets. The identity of the c-Kit protein was confirmed by immunoreactivity with an anti-c-Kit-specific antibody and by its characterization as a phosphotyrosine-containing protein. Under constitutive conditions, c-Kit was found to be tyrosine-phosphorylated and was associated with a 85-kDa phosphoprotein that could be a fragment of phosphatidylinositol 3-kinase. These data indicate the presence of a new platelet surface molecule that could function in platelet activation. We demonstrate that the secondary wave of platelet aggregation and serotonin secretion induced by epinephrine and ADP, but not by the thromboxane analog U46619, was augmented by KL/SCF. The effect of KL/SCF on epinephrine/ADP-induced platelet activation appeared to be mediated in part through the thromboxane pathway. These data suggest that KL/SCF could modulate hemostasis via interaction with platelets, particularly in conditions where mesenchymal cells are exposed to circulating blood elements, such as in wound healing or atherosclerosis.
Grabarek
J
J
Department of Medicine, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Groopman
J E
JE
Lyles
Y R
YR
Jiang
S
S
Bennett
L
L
Zsebo
K
K
Avraham
H
H
D000244:Adenosine Diphosphate / Q000494:pharmacology; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000302:isolation & purification / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D019089:Stem Cell Factor; D013929:Thromboxane B2 / Q000378:metabolism
D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D012701:Serotonin; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D004837:Epinephrine