Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk

The Journal of Biological Chemistry
Kevin C OrtonJ A Traugh

Abstract

The mitogen-activated protein kinase-interacting kinase 1 (Mnk1) is phosphorylated by caspase-cleaved protein kinase Pak2/gamma-PAK but not by Cdc42-activated Pak2. Phosphorylation of Mnk1 is rapid, reaching 1 mol/mol within 15 min of incubation with Pak2. A kinetic analysis of the phosphorylation of Mnk1 by Pak2 yields a K(m) of 0.6 microm and a V(max) of 14.9 pmol of (32)P/min/microg of Pak2. Two-dimensional tryptic phosphopeptide mapping of Mnk1 phosphorylated by Pak2 yields two distinct phosphopeptides. Analysis of the phosphopeptides by automated microsequencing and manual Edman degradation identified the sites in Mnk1 as Thr(22) and Ser(27). Mnk1, activated by phosphorylation with Erk2, phosphorylates the eukaryotic initiation factor (eIF) 4E and the eIF4G components of eIF4F. Phosphorylation of Mnk1 by Pak2 does not activate Mnk1, as measured with either eIF4E or eIF4F as substrate. Phosphorylation of Erk2-activated Mnk1 by Pak2 has no effect on phosphorylation of eIF4E but reduces phosphorylation of eIF4G by Mnk1 by up to 50%. Phosphorylation of Mnk1 by Pak2 inhibits binding of eIF4G peptides containing the Mnk1 binding site by up to 80%. When 293T cells are subjected to apoptotic induction by hydrogen peroxide, Mnk1 is...Continue Reading

References

Oct 1, 1989·The Journal of Cell Biology·R F Duncan, J W Hershey
Jun 16, 1995·The Journal of Biological Chemistry·B JoshiR E Rhoads
Mar 15, 1996·European Journal of Biochemistry·V M Pain
Aug 30, 1996·The Journal of Biological Chemistry·R D RooneyJ A Traugh
Oct 27, 1997·The Journal of Biological Chemistry·G C ScheperR van Wijk
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·N LeeL T Williams
Jan 31, 1998·The Journal of Biological Chemistry·R G VriesC G Proud
Mar 10, 1998·European Journal of Biochemistry·Y W Chang, J A Traugh
Apr 29, 1998·The Journal of Biological Chemistry·N J Richter-CookW C Merrick
Jul 8, 1998·European Journal of Biochemistry·M KleijnA A Thomas
Jan 19, 1999·Annual Review of Cell and Developmental Biology·N K Gray, M Wickens
Mar 19, 1999·Progress in Molecular and Subcellular Biology·E Manser, L Lim
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·L McKendrickS J Morley
Jun 29, 2000·Annual Review of Biochemistry·A C GingrasN Sonenberg
Oct 26, 2000·Trends in Genetics : TIG·M HolcikR G Korneluk
Nov 4, 2000·The Journal of Biological Chemistry·N L KorneevaR E Rhoads
May 11, 2001·Vitamins and Hormones·J Roig, J A Traugh
Apr 5, 2003·Annual Review of Biochemistry·Gary M Bokoch
Jul 11, 2003·The Journal of Biological Chemistry·Rolf JakobiDaniel K Stringer
Sep 2, 2003·The Journal of Biological Chemistry·Josep-Lluis Parra-PalauChristopher G Proud
Jan 30, 2004·Molecular and Cellular Biology·Zhongdong HuangJ Michael Bishop

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Citations

Jan 24, 2009·Cancer Metastasis Reviews·Bettina DummlerJeffrey Field
Feb 8, 2014·Nature Reviews. Cancer·Maria RaduJonathan Chernoff
Apr 18, 2012·Oncogene·Y MartineauS Pyronnet
May 19, 2005·Cell Death and Differentiation·S J MorleyM J Clemens
May 5, 2010·Proceedings of the National Academy of Sciences of the United States of America·Brion W MurrayTod Smeal
Nov 6, 2008·The Journal of Biological Chemistry·Yuan-Hao HsuJolinda A Traugh
Jul 21, 2006·Proteome Science·Frédéric Delom, Eric Chevet
Oct 2, 2007·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Carol A ChrestensenThomas W Sturgill
Mar 7, 2006·Journal of Neurochemistry·Gabriel RossWayne S Sossin
Nov 20, 2012·Cellular Logistics·Diana Zi Ye, Jeffrey Field
Nov 5, 2010·Molecular Cancer Research : MCR·Nadejda L KorneevaJun Chung
Sep 18, 2021·Journal of Medicinal Chemistry·Weijun XuKassoum Nacro

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