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.