Proviral Integration site for Moloney murine leukemia virus kinase family (PIM kinase family) (PIM)

The Proviral Integration site for Moloney murine leukemia virus (PIM) kinase family consists of three highly conserved serine/threonine kinases: PIM1, PIM2, and PIM3 (UniProt P11309, Q9P1W9, Q86V86). These kinases are unique because they are constitutively active and primarily regulated by their protein expression levels rather than post-translational modifications (PubMed: 25813493). They function as downstream effectors of the JAK/STAT signaling pathway and play pivotal roles in promoting cell survival, proliferation, and metabolism by phosphorylating a wide range of substrates, including BAD, p21, and 4E-BP1 (PubMed: 21306011). In many cancers, particularly hematologic malignancies and certain solid tumors like prostate and breast cancer, PIM kinases are overexpressed and contribute to tumor growth and resistance to chemotherapy or targeted therapies (PubMed: 24832511). Consequently, the PIM kinase family has emerged as a significant therapeutic target, with several pan-PIM and selective inhibitors like PIM447 and AZD1208 undergoing clinical evaluation to disrupt these oncogenic signaling nodes (ClinicalTrials.gov: NCT02078609). Their role in maintaining the stability of the MYC oncoprotein further underscores their importance as a target in MYC-driven malignancies (PubMed: 29138338).

Other names

PIM1PIM2PIM3Serine/threonine-protein kinase pim-1Serine/threonine-protein kinase pim-2Serine/threonine-protein kinase pim-3PIM kinase

ATP-competitive inhibition of PIM1, PIM2, and PIM3 kinases, which prevents the phosphorylation of downstream substrates such as BAD, p21, and 4E-BP1, thereby inducing apoptosis and inhibiting cell cycle progression (PubMed: 25813493).