Macrophage colony-stimulating factor receptor induces tyrosine phosphorylation of SKAP55R adaptor and its association with actin

Cell Signal. 2005 Aug;17(8):941-9. doi: 10.1016/j.cellsig.2004.11.009. Epub 2005 Jan 20.

Abstract

The production, survival, and function of monocytes and macrophages are regulated by the macrophage colony-stimulating factor (M-CSF or CSF-1) through its tyrosine kinase receptor. M-CSF receptor activates multiple cytoplasmic pathways in which adaptor and scaffolding proteins play a central role. In this study, we showed that SKAP55-related (SKAP55R) adaptor protein is expressed in myeloid cells and macrophages and is rapidly and transiently tyrosine-phosphorylated in response to M-CSF. M-CSF induced SKAP55R association with other tyrosine-phosphorylated proteins and with actin. When overexpressed in myeloid cells, SKAP55R decreased M-CSF-dependent proliferation without affecting differentiation. Altogether, these results demonstrate that SKAP55R adaptor is implicated in the M-CSF signaling pathway and suggest its role as a negative regulator of growth. Moreover, specific association between SKAP55R and actin support the idea that SKAP55R is implicated in the regulation of actin dynamics under the control of M-CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Lineage
  • Cell Proliferation
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology
  • Cytoplasm / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Gene Transfer Techniques
  • Green Fluorescent Proteins / metabolism
  • Growth Substances
  • Immunoblotting
  • Immunoprecipitation
  • Interleukin-3 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Macrophages / metabolism
  • Mice
  • Myeloid Cells / cytology
  • Myeloid Cells / metabolism
  • Phosphoproteins / chemistry*
  • Phosphorylation
  • Rats
  • Retroviridae / genetics
  • Signal Transduction
  • Tyrosine / chemistry
  • Tyrosine / metabolism*

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Culture Media, Conditioned
  • Growth Substances
  • Interleukin-3
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • src kinase associated phosphoprotein 2
  • Green Fluorescent Proteins
  • Tyrosine
  • Macrophage Colony-Stimulating Factor