Extracellular calcium mimics the actions of platelet-derived growth factor on mouse fibroblasts.
Microprecipitates of calcium phosphate (CaPO4) can substitute for platelet-derived growth factor (PDGF) to stimulate the growth of cultured 3T3 cells. In two-part complementation assays, CaPO4 behaves as a PDGF-like "competence factor"--that is, the mitogenic response to CaPO4 is enhanced synergistically by "progression factors" contained in platelet-poor plasma. In studies described here, we show that early cytoplasmic and intranuclear events in the mitogenic response to CaPO4 are equivalent to those induced by PDGF. However, no net increase in tyrosine kinase activity of either the PDGF-alpha or PDGF-beta receptor is seen following exposure to CaPO4. Our data suggest that calcium acts within the cell, regulating events which normally proceed from activation of PDGF receptors. Alternatively, microprecipitates of CaPO4 could act externally by activating a growth factor receptor which escapes detection with available reagents.
Epstein
R J
RJ
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Druker
B J
BJ
Irminger
J C
JC
Jones
S D
SD
Roberts
T M
TM
Stiles
C D
CD
D016475:3T3 Cells / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005796:Genes / Q000235:genetics / Q000502:physiology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D014162:Transfection / Q000235:genetics / Q000502:physiology
D002130:Calcium Phosphates; D010982:Platelet-Derived Growth Factor; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D019908:Proto-Oncogene Proteins c-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous