JAK2 and colonic neoplasm: However, TP53R172H may also increase JAK2/STAT3 signaling independent of gp130 cytokines through direct interaction with the gp130-associated phosphatase SHP2,17 reminiscent of the direct binding of the TP53R248Q protein to activated pSTAT3, thereby “short circuiting” the ligand dependency of the STAT3 signaling cascade during colon cancer progression.18