Colony-stimulating Factor-1 Stimulates the Formation of Multimeric Cytosolic Complexes of Signaling Proteins and Cytoskeletal Components in Macrophages

CSF-1 Receptor Signaling in Myeloid Cells

“…Signaling may also occur from internalized receptors (Huynh et al 2012). Many of the proteins in complexes with the rapidly tyrosine phosphorylated cellular proteins are cytoskeletal proteins (Yeung et al 1998;Yeung and Stanley 2003) and the short-term responses include extensive cytoskeletal remodeling (Boocock et al 1989;Pixley et al 2001;Chitu et al 2005;Sampaio et al 2011;Pixley 2012). Increased protein synthesis is detected as early as 15 min following CSF-1R stimulation and plateaus at 2 h (Tushinski and Stanley 1983).…”

“…CSF-1 binding initially leads to rapid dimerization, a first wave of tyrosine phosphorylation of the CSF-1R, and formation of CSF-1R complexes with Grb2/Sos and with SFK, Cbl, the regulatory subunit of PI-3 kinase (PI3K) ( p85), Grb2, and other signaling molecules, many of which become tyrosine phosphorylated (Baccarini et al 1991;Kanagasundaram et al 1996;Wang et al 1996Wang et al , 1999bHusson et al 1997). The tyrosine phosphorylated proteins, representing 0.02% of the total cellular protein, are mainly in the membrane fraction (Yeung et al 1998). The CSF-1R/Sos/Grb2 complexes are more transient than those involving the CSF-1R, Cbl, Shc, p85, and Grb2 (Wang et al 1999b).…”

Paxillin: Adapting to Change

“…Paxillin and Hic-5 also bind to the syndecan binding protein syndesmos (52), Hsp27 (118), Hsp72 (172), and the ring-finger ubiquitination component Rnf5 (54). Other studies have reported the coprecipitation of paxillin in complexes that contain ␥-sarcoglycan (320), the tyrosine phosphatases SHP-1/2 (318), phospholipase D (113), STAT transcription factors, and translation elongation factor-1␣ (318). Characterization of the molecular basis of these associations so that discrete perturbation of paxillin binding can be effected will allow for the determination of the physiological consequences in forming these interactions.…”

Macrophage Colony-stimulating Factor Promotes Cell Survival through Akt/Protein Kinase B

“…M-CSF dimers cross-link two tyrosine kinase M-CSF receptors (also known as FMS or colony-stimulating factor-1 receptors), inducing autoand transphosphorylation of tyrosine residues in the cytoplasmic domains of these receptors (11). Phosphotyrosine residues in the cytoplasmic domains of M-CSF receptors induce translocation of intracellular signaling molecules via SH2 interactions and activate signaling cascades, resulting in the activation of both PI3K-dependent and Ras/mitogen-activated protein kinase-dependent pathways (12). Similar to normal human monocytes, NIH 3T3 fibroblasts transfected with the gene encoding the human M-CSF receptor (FMS gene) also activate these intracellular signaling pathways in response to human M-CSF (13).…”