Mh. Wang et al., MACROPHAGE-STIMULATING PROTEIN INDUCES PROLIFERATION AND MIGRATION OFMURINE KERATINOCYTES, Experimental cell research, 226(1), 1996, pp. 39-46
Macrophage stimulating protein (MSP) is a chemotactic factor for murin
e peritoneal macrophages. The receptor for human MSP was recently iden
tified as the ron gene product, a transmembrane protein tyrosine kinas
e cloned from a human keratinocyte cDNA library. Here we report that M
SP induced proliferation of murine primary keratinocytes and establish
ed keratinocyte cell lines in a concentration-dependent manner. The gr
owth 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 sp
ecific binding of MSP to the STK gene product, a murine homologue of t
he RON MSP receptor. Binding of MSP to keratinocyte STK induced phosph
orylation of the 150 kDa STK beta chain. Herbimycin A, a protein tyros
ine kinase inhibitor, blocked MSP-mediated phosphorylation of the STK
receptor as well as proliferation of keratinocytes, suggesting the imp
ortance of tyrosine kinase activity for transduction of the message de
livered by MSP. Previously, the only known target cell for MSP was the
resident peritoneal macrophage. These studies establish the keratinoc
yte as a new target cell for MSP. The action of MSP on keratinocytes m
ay have implications for tissue repair, wound healing, and tumor growt
h. (C) 1996 Academic Press, Inc.