Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclast-like cells

Noriyoshi Kurihara, Atsushi Iwama, Junichi Tatsumi, Katsumi Ikeda, Toshio Suda

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Recently we cloned a novel receptor tyrosine kinase, STK. STK belongs to the hepatocyte growth factor receptor family and was identified as the receptor for macrophage-stimulating protein (MSP). STK is expressed on a restricted macrophage population such as peritoneal macrophages, but not on mononuclear phagocytes of peripheral blood, bone marrow, or alveoli. Using an anti-STK monoclonal antibody, we observed STK expression on multinuclear osteoclast-like cells (OCLs) formed by murine bone marrow cultures in the presence of 1,25-dihydroxyvitamin D3 and interleukin-3. The OCLs expressed both the calcitonin receptor and STK. We also detected STK expression in bone-derived mouse osteoclasts. The addition of MSP to OCLs induced rapid morphologic changes such as cytoplasmic contraction and formation of ruffled border. In addition, MSP caused rapid redistribution of src to the borders of cytoplasm. These phenomena were associated with enhanced bone resorption. MSP caused a threefold increase in pit formation compared with control OCLs. These findings suggest that by involving src kinase, the MSP/STK signal transduction pathway induces rapid cytoskeletal reorganization in osteoclasts and facilitates bone resorption by osteoclasts.

Original languageEnglish (US)
Pages (from-to)3704-3710
Number of pages7
JournalBlood
Volume87
Issue number9
StatePublished - May 1 1996
Externally publishedYes

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Receptor Protein-Tyrosine Kinases
Osteoclasts
Bone Resorption
Bone
Macrophages
Bone Marrow
Calcitonin Receptors
Proto-Oncogene Proteins c-met
Signal transduction
src-Family Kinases
Calcitriol
Interleukin-3
Peritoneal Macrophages
Phagocytes
macrophage stimulating protein
Signal Transduction
Cytoplasm
Blood
Monoclonal Antibodies
Bone and Bones

ASJC Scopus subject areas

  • Hematology

Cite this

Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclast-like cells. / Kurihara, Noriyoshi; Iwama, Atsushi; Tatsumi, Junichi; Ikeda, Katsumi; Suda, Toshio.

In: Blood, Vol. 87, No. 9, 01.05.1996, p. 3704-3710.

Research output: Contribution to journalArticle

Kurihara, Noriyoshi ; Iwama, Atsushi ; Tatsumi, Junichi ; Ikeda, Katsumi ; Suda, Toshio. / Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclast-like cells. In: Blood. 1996 ; Vol. 87, No. 9. pp. 3704-3710.
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