In the process of colitis development, IL-6 binds to soluble or membrane-bound IL-6 receptor (IL-6R) polypeptides that signal by interacting with the membrane-associated gp130 subunit, whose engagement triggers the activation of Janus kinases (JAKs), the downstream effectors of STAT3, Shp2-Ras, and phosphatidylinositol 3-kinase (PI3K)-Akt [30]. Here, PTPN11 is linked to colitis.