Molecular Basis of MAP Kinase Regulation

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2013 Oct 12

PMID 24115095

Citations 140

Authors

Wolfgang Peti

Rebecca Page

Affiliations

Soon will be listed here.

Abstract

Mitogen-activated protein kinases (MAPKs; ERK1/2, p38, JNK, and ERK5) have evolved to transduce environmental and developmental signals (growth factors, stress) into adaptive and programmed responses (differentiation, inflammation, apoptosis). Almost 20 years ago, it was discovered that MAPKs contain a docking site in the C-terminal lobe that binds a conserved 13-16 amino acid sequence known as the D- or KIM-motif (kinase interaction motif). Recent crystal structures of MAPK:KIM-peptide complexes are leading to a precise understanding of how KIM sequences contribute to MAPK selectivity. In addition, new crystal and especially NMR studies are revealing how residues outside the canonical KIM motif interact with specific MAPKs and contribute further to MAPK selectivity and signaling pathway fidelity. In this review, we focus on these recent studies, with an emphasis on the use of NMR spectroscopy, isothermal titration calorimetry and small angle X-ray scattering to investigate these processes.

Citing Articles

The MAPK/ERK signaling pathway involved in Raddeanin A induces apoptosis via the mitochondrial pathway and G2 phase arrest in multiple myeloma.

Jiang M, Li C, Mao C, Yu H, Zhou Y, Pu S Sci Rep. 2024; 14(1):29061.

PMID: 39580496 PMC: 11585587. DOI: 10.1038/s41598-024-76465-z.

Fas Apoptosis Inhibitory Molecule 2 Inhibits Pathological Cardiac Hypertrophy by Regulating the MAPK Signaling Pathway.

Zhong H, Wu M, Xie H, Chen X, Li J, Duan Z J Am Heart Assoc. 2024; 13(22):e034257.

PMID: 39547961 PMC: 11681402. DOI: 10.1161/JAHA.124.034257.

Exploring the Role of Licorice and Its Derivatives in Cell Signaling Pathway NF-B and MAPK.

Fatima I, Sahar A, Tariq A, Naz T, Usman M J Nutr Metab. 2024; 2024:9988167.

PMID: 39479405 PMC: 11524698. DOI: 10.1155/2024/9988167.

Special Issue: MAPK Signaling Cascades in Human Health and Diseases.

Seger R Int J Mol Sci. 2024; 25(20).

PMID: 39457006 PMC: 11509016. DOI: 10.3390/ijms252011226.

Immunostimulatory Effect of Ovomucin Hydrolysates by Pancreatin in RAW 264.7 Macrophages via Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway.

Jang J, Lee J, Kim K, Ahn D, Paik H Food Sci Anim Resour. 2024; 44(4):885-898.

PMID: 38974730 PMC: 11222692. DOI: 10.5851/kosfa.2024.e25.

References

Bardwell A, Frankson E, Bardwell L . Selectivity of docking sites in MAPK kinases. J Biol Chem. 2009; 284(19):13165-73. PMC: 2676048. DOI: 10.1074/jbc.M900080200. View

Saxena M, Williams S, Tasken K, Mustelin T . Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase. Nat Cell Biol. 1999; 1(5):305-11. DOI: 10.1038/13024. View

Cuadrado A, Nebreda A . Mechanisms and functions of p38 MAPK signalling. Biochem J. 2010; 429(3):403-17. DOI: 10.1042/BJ20100323. View

Hendriks W, Schepens J, Brugman C, Zeeuwen P, Wieringa B . A novel receptor-type protein tyrosine phosphatase with a single catalytic domain is specifically expressed in mouse brain. Biochem J. 1995; 305 ( Pt 2):499-504. PMC: 1136390. DOI: 10.1042/bj3050499. View

Kim S, Hahn J, Min Y, Yoo N, Ko Y, Lee W . Constitutive activation of extracellular signal-regulated kinase in human acute leukemias: combined role of activation of MEK, hyperexpression of extracellular signal-regulated kinase, and downregulation of a phosphatase, PAC1. Blood. 1999; 93(11):3893-9. View

White A, Pargellis C, Studts J, Werneburg B, Farmer 2nd B . Molecular basis of MAPK-activated protein kinase 2:p38 assembly. Proc Natl Acad Sci U S A. 2007; 104(15):6353-8. PMC: 1851067. DOI: 10.1073/pnas.0701679104. View

Garai A, Zeke A, Gogl G, Toro I, Fordos F, Blankenburg H . Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove. Sci Signal. 2012; 5(245):ra74. PMC: 3500698. DOI: 10.1126/scisignal.2003004. View

Yang S, Galanis A, Sharrocks A . Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors. Mol Cell Biol. 1999; 19(6):4028-38. PMC: 104362. DOI: 10.1128/MCB.19.6.4028. View

Tao X, Tong L . Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5. Protein Sci. 2007; 16(5):880-6. PMC: 2206639. DOI: 10.1110/ps.062712807. View

10.

OConnell N, Nichols S, Heroes E, Beullens M, Bollen M, Peti W . The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme. Structure. 2012; 20(10):1746-56. PMC: 3472097. DOI: 10.1016/j.str.2012.08.003. View

11.

Laughlin J, Nwachukwu J, Figuera-Losada M, Cherry L, Nettles K, LoGrasso P . Structural mechanisms of allostery and autoinhibition in JNK family kinases. Structure. 2012; 20(12):2174-84. PMC: 3589125. DOI: 10.1016/j.str.2012.09.021. View

12.

Piserchio A, Francis D, Koveal D, Dalby K, Page R, Peti W . Docking interactions of hematopoietic tyrosine phosphatase with MAP kinases ERK2 and p38α. Biochemistry. 2012; 51(41):8047-9. PMC: 3548032. DOI: 10.1021/bi3012725. View

13.

Lee T, Hoofnagle A, Kabuyama Y, Stroud J, Min X, Goldsmith E . Docking motif interactions in MAP kinases revealed by hydrogen exchange mass spectrometry. Mol Cell. 2004; 14(1):43-55. DOI: 10.1016/s1097-2765(04)00161-3. View

14.

Patterson K, Brummer T, OBrien P, Daly R . Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J. 2009; 418(3):475-89. DOI: 10.1042/bj20082234. View

15.

Gogl G, Toro I, Remenyi A . Protein-peptide complex crystallization: a case study on the ERK2 mitogen-activated protein kinase. Acta Crystallogr D Biol Crystallogr. 2013; 69(Pt 3):486-9. PMC: 3605046. DOI: 10.1107/S0907444912051062. View

16.

Saxena M, Williams S, Brockdorff J, Gilman J, Mustelin T . Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP). J Biol Chem. 1999; 274(17):11693-700. DOI: 10.1074/jbc.274.17.11693. View

17.

Lukas S, Kroe R, Wildeson J, Peet G, Frego L, Davidson W . Catalysis and function of the p38 alpha.MK2a signaling complex. Biochemistry. 2004; 43(31):9950-60. DOI: 10.1021/bi049508v. View

18.

Tarrega C, Blanco-Aparicio C, Munoz J, Pulido R . Two clusters of residues at the docking groove of mitogen-activated protein kinases differentially mediate their functional interaction with the tyrosine phosphatases PTP-SL and STEP. J Biol Chem. 2001; 277(4):2629-36. DOI: 10.1074/jbc.M108874200. View

19.

Nielsen G, Schwalbe H . NMR spectroscopic investigations of the activated p38α mitogen-activated protein kinase. Chembiochem. 2011; 12(17):2599-607. DOI: 10.1002/cbic.201100527. View

20.

Kumar G, Zettl H, Page R, Peti W . Structural basis for the regulation of the mitogen-activated protein (MAP) kinase p38α by the dual specificity phosphatase 16 MAP kinase binding domain in solution. J Biol Chem. 2013; 288(39):28347-56. PMC: 3784751. DOI: 10.1074/jbc.M113.499178. View