Colony-stimulating factor-1 stimulates the formation of multimeric cytosolic complexes of signaling proteins and cytoskeletal components in macrophages

Yee Guide Yeung, Yun Wang, Douglas B. Einstein, Pierre S.W. Lee, E. Richard Stanley

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Stimulation of macrophages with colony-stimulating factor-1 (CSF-1) results in the protein tyrosine phosphorylation of the CSF-1 receptor (CSF- 1R) and many other, primarily cytosolic, proteins. Stimulation by CSF-1 at 4 °C was used to facilitate the purification and identification of the proteins of the cytosolic anti-phosphotyrosine (PY)-reactive fraction (αPY- RF) involved in downstream signaling pathways. Confocal microscopy revealed that the PY proteins are in close proximity to the CSF-1R at the plasma membrane. The αPY-RF contained pre-existing complexes of PY proteins and non-PY proteins which generally increased in size and PY protein content following CSF-1 stimulation. PY proteins identified by microsequencing and Western blotting include Cbl, STAT3, STAT5a, STAT5b, SHP-1, Shc, and two novel proteins pp57 and pp37. Other proteins included cytoskeletal/contractile proteins (paxillin, vimentin, elongation factor- 1α, F-actin, tropomyosin, and myosin regulatory light chain), Ras family signaling proteins (p85 (phosphoinositide 3-kinase), Vav, Ras-GTPase- activating protein SH3 domain-binding protein, and Grb2), DnaJ-like protein, and glyceraldehyde-3-phosphate dehydrogenase. CSF-1 induced the de novo recruitment of Cbl, STAT3, STAT5a, STAT5b, p85, SHP-1, Shc, vimentin, and Grb2 to complexes and caused preexisting complexes involving Vav, elongation factor-1α, and F-actin to increase in size. These studies indicate that CSF- l-induced protein tyrosine phosphorylation is associated with the reorganization of complexes of cytoskeletal, signaling, and other proteins that mediate CSF-l-regulated motility and growth.

Original languageEnglish (US)
Pages (from-to)17128-17137
Number of pages10
JournalJournal of Biological Chemistry
Volume273
Issue number27
DOIs
StatePublished - Jul 3 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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