The PIM (Proviral Insertion site in Moloney murine leukemia virus) family includes the serine/threonine kinases PIM-1, PIM-2, and PIM-3.
The expression of PIM kinases is regulated largely through upstream JAK-STAT signaling.
PIM kinases bind to and stabilize the oncoprotein MYC, which plays a crucial role in cell cycle regulation.
PIM kinases phosphorylate a number of target molecules, several of which are common substrates with the PI3K/AKT pathway, including:
• Activation of the mTORC1 complex, a key effector of the PI3K pathway that promotes cell survival.
• Modifications of the ribosome-associated protein targets p70S6K and 4EBP, leading to increased protein synthesis.
• Inhibition of the pro-apaptotic protein BAD, reducing cell death.
Dysregulated PIM activity may enhance cancer cell proliferation and survival in a variety of hematological malignancies and solid tumors.