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Function
Proto-oncogene serine/threonine-protein kinase (Pim1) is the provirus integration site for Moloney murine leukemia virus 1[1]. Pim1 is involved in cell cycle progression, apoptosis, transcriptional activation and signaling pathways. Pim1 phosphorylates and inhibits proapoptotic proteins. For details see Student Project 6 for UMass Chemistry 423 Spring 2015. See also Oncogenes & Tumor Suppressor Genes.
- Chk1 or checkpoint kinase 1 phosphorylates variety of proteins resulting in activation of DNA damage checkpoint and more[2].
- Chk2 or checkpoint kinase 2 has a role in cell cycle arrest and apoptosis by DNA damage [3].
- Plk1 or Polo-like kinase 1 phosphorylates variety of proteins affecting cell entry into mitosis, centrosome maturation, spindle assembly and cytokinesis[4].
- Plk3 or Polo-like kinase 3 becomes phosphorylated after DNA damage or mitotic spindle disruption [5].
- Haspin phosphorylates histone H3 and thus affects mitosis [6].
- mTOR or mechanistic target of rapamycin signaling influences longevity and aging [7].
- LRRK1, LRRK2 or leucine-rich repeat kinase phosphorylate Rab proteins [8].
- RIP regulates apoptosis[9].
- Ulk1, Ulk2 play a role in activating autophagy in mammals[10].
- Hipa phosphorylates Glu-tRNA synthetase causing bacterial antibiotic persistence [11].
Relevance
Pim1 is a progression marker in diffuse large B-cell lymphoma[12].
Disease
Pim-1 plays a pivotal role in several tumor relevant signaling pathways and is relevant to colon carcinoma[13].
Structural highlights
Pim1 is phosphorylated on serine 261 (PSer). The consensus peptide (pimtide) ARKRRRHPSGPPTA binds strongly to Pim1[14]. Water molecules are shown as red spheres.
pim-1 3D structures
Proto-oncogene serine/threonine protein kinase 3D structures
- ↑ Bachmann M, Moroy T. The serine/threonine kinase Pim-1. Int J Biochem Cell Biol. 2005 Apr;37(4):726-30. PMID:15694833 doi:https://dx.doi.org/10.1016/j.biocel.2004.11.005
- ↑ Patil M, Pabla N, Dong Z. Checkpoint kinase 1 in DNA damage response and cell cycle regulation. Cell Mol Life Sci. 2013 Nov;70(21):4009-21. PMID:23508805 doi:10.1007/s00018-013-1307-3
- ↑ Ahn J, Urist M, Prives C. The Chk2 protein kinase. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1039-47. PMID:15279791 doi:10.1016/j.dnarep.2004.03.033
- ↑ Iliaki S, Beyaert R, Afonina IS. Polo-like kinase 1 (PLK1) signaling in cancer and beyond. Biochem Pharmacol. 2021 Nov;193:114747. PMID:34454931 doi:10.1016/j.bcp.2021.114747
- ↑ Bahassi el M, Conn CW, Myer DL, Hennigan RF, McGowan CH, Sanchez Y, Stambrook PJ. Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways. Oncogene. 2002 Sep 26;21(43):6633-40. PMID:12242661 doi:10.1038/sj.onc.1205850
- ↑ Kestav K, Uri A, Lavogina D. Structure, Roles and Inhibitors of a Mitotic Protein Kinase Haspin. Curr Med Chem. 2017;24(21):2276-2293. PMID:28413956 doi:10.2174/0929867324666170414155520
- ↑ Weichhart T. mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review. Gerontology. 2018;64(2):127-134. PMID:29190625 doi:10.1159/000484629
- ↑ Malik AU, Karapetsas A, Nirujogi RS, Mathea S, Chatterjee D, Pal P, Lis P, Taylor M, Purlyte E, Gourlay R, Dorward M, Weidlich S, Toth R, Polinski NK, Knapp S, Tonelli F, Alessi DR. Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms. Biochem J. 2021 Feb 12;478(3):553-578. PMID:33459343 doi:10.1042/BCJ20200937
- ↑ Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ, Leder P. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity. 1998 Mar;8(3):297-303. PMID:9529147 doi:10.1016/s1074-7613(00)80535-x
- ↑ Chan EY, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol. 2009 Jan;29(1):157-71. doi: 10.1128/MCB.01082-08. Epub 2008 Oct, 20. PMID:18936157 doi:https://dx.doi.org/10.1128/MCB.01082-08
- ↑ Kaspy I, Rotem E, Weiss N, Ronin I, Balaban NQ, Glaser G. HipA-mediated antibiotic persistence via phosphorylation of the glutamyl-tRNA-synthetase. Nat Commun. 2013;4:3001. PMID:24343429 doi:10.1038/ncomms4001
- ↑ Brault L, Menter T, Obermann EC, Knapp S, Thommen S, Schwaller J, Tzankov A. PIM kinases are progression markers and emerging therapeutic targets in diffuse large B-cell lymphoma. Br J Cancer. 2012 Jul 24;107(3):491-500. doi: 10.1038/bjc.2012.272. Epub 2012 Jun, 21. PMID:22722314 doi:https://dx.doi.org/10.1038/bjc.2012.272
- ↑ Weirauch U, Beckmann N, Thomas M, Grunweller A, Huber K, Bracher F, Hartmann RK, Aigner A. Functional role and therapeutic potential of the pim-1 kinase in colon carcinoma. Neoplasia. 2013 Jul;15(7):783-94. PMID:23814490
- ↑ Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S, Bracher F. 7,8-Dichloro-1-oxo-beta-carbolines as a Versatile Scaffold for the Development of Potent and Selective Kinase Inhibitors with Unusual Binding Modes. J Med Chem. 2012 Jan 12;55(1):403-13. Epub 2012 Jan 3. PMID:22136433 doi:10.1021/jm201286z
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