Reactome | Inactivation of CSF3 (G-CSF) signaling

Inactivation of CSF3 (G-CSF) signaling

Stable Identifier

R-HSA-9705462

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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
14512302	Receptor activation and 2 distinct COOH-terminal motifs control G-CSF receptor distribution and internalization kinetics Roovers, O, Aarts, LH, Ward, AC, Touw, IP	Blood	2004
23276911	Scratching the surface: signaling and routing dynamics of the CSF3 receptor Meenhuis, A, Palande, K, Jevdjovic, T, Touw, IP	Front Biosci (Landmark Ed)	2013
12133942	Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony stimulating factor receptor and modulates its signal transduction Johnston, JA, Nielsch, U, Haan, S, Hörtner, M, Mayr, LM, Heinrich, PC	J Immunol	2002
20237318	G-CSF and its receptor in myeloid malignancy Touw, IP, Beekman, R	Blood	2010
19453968	Site-specific ubiquitination determines lysosomal sorting and signal attenuation of the granulocyte colony-stimulating factor receptor Irandoust, M, Roovers, O, Meenhuis, A, Gits, J, Touw, IP, Wölfler, A	Traffic	2009
9885206	Defective internalization and sustained activation of truncated granulocyte colony-stimulating factor receptor found in severe congenital neutropenia/acute myeloid leukemia Schelen, AM, Ward, AC, Touw, IP, van Aesch, YM	Blood	1999
15107455	Distinct activities of suppressor of cytokine signaling (SOCS) proteins and involvement of the SOCS box in controlling G-CSF signaling Gits, J, van de Geijn, GJ, Touw, IP	J Leukoc Biol	2004
17363902	Suppressor of cytokine signaling 3 controls lysosomal routing of G-CSF receptor Irandoust, MI, Roovers, O, Aarts, LH, Gits, J, Erkeland, SJ, Touw, IP	EMBO J	2007