THE MURINE STK GENE-PRODUCT, A TRANSMEMBRANE PROTEIN-TYROSINE KINASE,IS A RECEPTOR FOR MACROPHAGE-STIMULATING PROTEIN

Macrophage stimulaling protein (MSP) was originally identified as an i nducer of murine resident peritoneal macrophage responsiveness to chem oattractants. We recently showed that the product of RON, a protein ty rosine kinase cloned from a human keratinocyte library, is the recepto r for MSP, Similarity of murine stk to RON led us to determine if the stk gene product is the murine receptor for MSP. Radiolabeled MSP coul d bind to NIH 3T3 cells transfected with murine stk cDNA (3T3/stk), Bi nding was saturable and was inhibited by unlabeled MSP but not by stru cturally related proteins, including hepatocyte growth factor and plas minogen, Specific binding to STK was demonstrated by cross-linking of I-125-labeled MSP to membrane proteins of 3T3/stk cells, which resulte d in a protein complex with a molecular mass of 220 kDa, This radiolab eled complex comprised I-125-MSP and STK, since it could be immunoprec ipitated by antibodies to the STK beta chain. Binding of MSP to stk cD NA-transfected cells induced tyrosine phosphorylation of the 150-kDa S TK beta chain within 1 min and caused increased motile activity. These results establish the murine stk gene product as a specific transmemb rane protein tyrosine kinase receptor for MSP, Inasmuch as the stk cDN A was cloned from a hematopoietic stem cell, our data suggest that in addition to macrophages and keratinocytes, a cell in the hematopoietic lineage may also be a target for MSP.