Macrophage-stimulating protein induces proliferation and migration of murine keratinocytes.
Macrophage stimulating protein (MSP) is a chemotactic factor for murine peritoneal macrophages. The receptor for human MSP was recently identified as the ron gene product, a transmembrane protein tyrosine kinase cloned from a human keratinocyte cDNA library. Here we report that MSP induced proliferation of murine primary keratinocytes and established keratinocyte cell lines in a concentration-dependent manner. The growth efficacy of MSP was comparable to that of epidermal growth factor and keratinocyte growth factor. In three of four cell lines tested in a chemotaxis chamber, MSP also stimulated migration of keratinocytes on a collagen type IV substratum. The action of MSP was mediated by specific binding of MSP to the STK gene product, a murine homologue of the RON MSP receptor. Binding of MSP to keratinocyte STK induced phosphorylation of the 150 kDa STK beta chain. Herbimycin A, a protein tyrosine kinase inhibitor, blocked MSP-mediated phosphorylation of the STK receptor as well as proliferation of keratinocytes, suggesting the importance of tyrosine kinase activity for transduction of the message delivered by MSP. Previously, the only known target cell for MSP was the resident peritoneal macrophage. These studies establish the keratinocyte as a new target cell for MSP. The action of MSP on keratinocytes may have implications for tissue repair, wound healing, and tumor growth.
Wang
M H
MH
Laboratory of Immunobiology, National Cancer Institute and Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA.
Dlugosz
A A
AA
Sun
Y
Y
Suda
T
T
Skeel
A
A
Leonard
E J
EJ
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor; D006801:Humans; D007457:Iodine Radioisotopes; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D010766:Phosphorylation; D011498:Protein Precursors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D006133:Growth Substances; D007457:Iodine Radioisotopes; D008934:Mitogens; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C082332:macrophage stimulating protein; D014443:Tyrosine; D017228:Hepatocyte Growth Factor; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases