Inactivation of CSF3 (G-CSF) signaling

Stable Identifier
R-HSA-9705462
Type
Pathway
Species
Homo sapiens
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Signaling by CSF3 causes its own inactivation, thereby preventing overproliferation of neutrophils (reviewed in Beekman and Touw 2010, Palande et al. 2013). Activated CSF3R recruits and activates JAK2, which phosphorylates STAT1, STAT3, and STAT5. The phosphorylated STATs transit to the nucleus and enhance the expression of SOCS1 and SOCS3, inhibitors of CSF3R signaling (inferred from mouse homologs). SOCS3, the principle negative regulator, binds the phosphorylated C-terminal region of CSF3R (Hörtner et al. 2002, van de Geijn et al. 2004, and inferred from mouse homologs) and acts in two ways: direct inhibition of the phosphorylation activity of JAK2 (van de Geijn et al. 2004) and promotion of endocytosis (Ward et al. 1999, Aarts et al. 2004, Irandoust et al. 2007) and ubiquitination (Irandoust et al. 2007, Wölfler et al. 2009) of CSF3R.

Literature References
PubMed ID Title Journal Year
23276911 Scratching the surface: signaling and routing dynamics of the CSF3 receptor

Palande, K, Meenhuis, A, Jevdjovic, T, Touw, IP

Front Biosci (Landmark Ed) 2013
14512302 Receptor activation and 2 distinct COOH-terminal motifs control G-CSF receptor distribution and internalization kinetics

Aarts, LH, Roovers, O, Ward, AC, Touw, IP

Blood 2004
12133942 Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony stimulating factor receptor and modulates its signal transduction

Hörtner, M, Nielsch, U, Mayr, LM, Johnston, JA, Heinrich, PC, Haan, S

J Immunol 2002
20237318 G-CSF and its receptor in myeloid malignancy

Beekman, R, Touw, IP

Blood 2010
19453968 Site-specific ubiquitination determines lysosomal sorting and signal attenuation of the granulocyte colony-stimulating factor receptor

Wölfler, A, Irandoust, M, Meenhuis, A, Gits, J, Roovers, O, Touw, IP

Traffic 2009
9885206 Defective internalization and sustained activation of truncated granulocyte colony-stimulating factor receptor found in severe congenital neutropenia/acute myeloid leukemia

Ward, AC, van Aesch, YM, Schelen, AM, Touw, IP

Blood 1999
15107455 Distinct activities of suppressor of cytokine signaling (SOCS) proteins and involvement of the SOCS box in controlling G-CSF signaling

van de Geijn, GJ, Gits, J, Touw, IP

J Leukoc Biol 2004
17363902 Suppressor of cytokine signaling 3 controls lysosomal routing of G-CSF receptor

Irandoust, MI, Aarts, LH, Roovers, O, Gits, J, Erkeland, SJ, Touw, IP

EMBO J 2007
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