Abstract
Protein kinase B (PKB) is a member of the second messenger-regulated subfamily of protein kinases, and plays a key role in cell-cycle regulation, glucose uptake and promotion of cell differentiation. Evidence shows that PKB undergoes activation in some human tumors and is involved in Ras pathway, which implies that PKB can trigger a pathway to induce oncogenic transformation. A nucleotide sequence of mousePkbγ was used as a probe to screen homolog in a human liver cDNA library. A fragment of 1998 bp containing a 1440 bp ORF encoding 479 amino acid residues was obtained. Then the 3′-terminal of this fragment was extended to 2788 bp by ‘electronic walking’ screening, and the extended fragment was confirmed by PCR amplification. The protein deduced by the gene had a high identity of 83% and 78% to the human PKBα and β, respectively, and was designated as humanPKBγ. Northern hybridization detected two equally expressed transcripts of 8.5 and 6.5 kb in length in all 16 human tissues tested, with the highest expression level in brain, and lower levels with variation in the other tissues. By RH mapping, thePKBγ was placed on chromosome 1q43, between markers D1S304 and D1S2693. It is a valuable clue for cloning the candidate genes related to prostate cancer; Arrhythmogenic Right Ventricular Dysplasia (ARVD); Chediak-Higashi, NK cell Deficiency (CHS); and Hypoparathyrodism with Short Stature, Mental Retardation and Seizures which have already been mapped in this chromosomal region.
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References
Meier, R., Hemmings, B. A., Regulation of protein kinase B, J. Recept Signal Transduct Res., 1999, 19(1-4): 121.
Marte, B. M., Downward, J., PKB/Akt: connecting phosphionositide 3-kinase to cell survival and beyond, TIBS, 1997, 22: 355.
Andjelkovic, M., Jakubowicz, T., Cron, P. et al., Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors, Proc. Natl. Acad. Sci. USA, 1996, 93: 5699.
Alessi, D. R., Cohen, P., Mechanism of activation and funcion of protein kinase B, Cum. Opin. Genet. Dev., 1998, 8(1): 55.
Konishi, H., Matsuzaki, H., Tanaka, M. et al., Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase, Proc. Natl. Acad. Sci. USA, 1996, 93: 7639.
Coffer, P. J., Jin, J., Woodgett, J. R., Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activaton, Biochem. J., 1998, 335(Pt 1): 1.
Downward, J., Mechanisms and consequences of activation of protein kinase B/Akt, Cum. Opin. Cell. Biol., 1998, 10(2): 262.
Kelley, T. W., Graham, M. M., Doseff, A. I. et al., Macrophage colony-stimulating factor promotes cell survival through AkVProtein kinase B, J. Biol. Chem., 1999, 274: 26393.
Cheng, J. Q., Ruggeri, B., Klein, W. M. et al., Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA, Proc. Natl. Acad. Sci. USA, 1996, 93(8): 3636.
Bos, J. L., A target for phosphoinositide 3-kinase: Akt/PKB, TIBS, 1995, 20: 441.
Jones, P. F., Jakubowicz, T., Pitossi, F. J. et al., Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily, Proc. Natl. Acad. Sci. USA, 1991, 88: 4171.
Jones, P. F., Jakubowicz, T., Hemmings, B. A., Molecular cloning of a second form of rac protein kinase, Cell Regulation, 1991, 2: 1001.
Konishi, H., Shinomura, T., Kuroda, S. et al., Molecular cloning of rat RAC protein kinase a and P and their association with protein kinase C ζ, Biochem. Biophys. Res. Commun., 1994, 205: 817.
Konishi, H., Kuroda, S., Tanaka, M. et al., Molecular cloning and characterization of a new member of the RAC protein kinase family: association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and βγ subunits of G proteins, Biochem. Biophys. Res. Commun., 1995, 216: 526.
Khwaja, A., Rodriguez-Viciana, P., Wennstrom, S. et al., Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinaseB/Akt cellular survival pathway, EMBO J., 1997, 16: 2783.
Kohn, A. D., Summers, S. A., Birnbaum, M. J. et al., Expression of a constitutively active Akt SerRhr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation, J. Biol. Chem., 1996, 271: 31372.
Mckusick, V. A. (translated by Luo Huiyuan et al.), Mendelian Inheritance in Man, Catalog of Human Gene and Hereditary Disease, 11st Version (1st Chinese version), Combined Publishing House of Beijing Medical University and Xiehe Medical University of China, 1997, p. 1454.
Berthon, P., Valeri, A., Cohen-Akenine, A. et al., Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2–43, Am. J. Hum. Genet., 1998, 62: 1416.
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Lan, F., Yu, L., Hu, P. et al. Cloning, tissue expression pattern, and chromosome localization of human protein kinase Bγ gene. Chin.Sci.Bull. 45, 1832–1839 (2000). https://doi.org/10.1007/BF02886289
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DOI: https://doi.org/10.1007/BF02886289