The murine stk gene product, a transmembrane protein tyrosine kinase, is a receptor for macrophage-stimulating protein

Ming Hai Wang, Atsushi Iwama, Alison Skeel, Toshio Suda, Edward J. Leonard

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Macrophage-stimulating protein (MSP) was originally identified as an inducer of murine resident peritoneal macrophage responsiveness to chemoattractants. We recently showed that the product of RON, a protein tyrosine kinase cloned from a human keratinocyte library, is the receptor 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 could bind to NIH 3T3 cells transfected with murine stk cDNA (3T3/stk). Binding was saturable and was inhibited by unlabeled MSP but not by structurally related proteins, including hepatocyte growth factor and plasminogen. Specific binding to STK was demonstrated by cross-linking of 125I-labeled MSP to membrane proteins of 3T3/stk cells, which resulted in a protein complex with a molecular mass of 220 kDa. This radiolabeled complex comprised 125I-MSP and STK, since it could be immunoprecipitated by antibodies to the STK β chain. Binding of MSP to stk cDNA-transfected cells induced tyrosine phosphorylation of the 150- kDa STK β chain within I min and caused increased motile activity. These results establish the murine stk gene product as a specific transmembrane protein tyrosine kinase receptor for MSP. Inasmuch as the stk cDNA 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.

Original languageEnglish
Pages (from-to)3933-3937
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number9
DOIs
Publication statusPublished - 1995 Apr 25

Keywords

  • hematopoietic stem cell
  • kringle
  • phosphorylation
  • receptor binding
  • transfection

ASJC Scopus subject areas

  • General

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