M H Cobb

Summary

Affiliation: University of Texas Southwestern Medical Center
Country: USA

Publications

  1. ncbi request reprint WNK1 activates ERK5 by an MEKK2/3-dependent mechanism
    Bing E Xu
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 279:7826-31. 2004
  2. ncbi request reprint Expression and characterization of MAP kinases in bacteria
    Charles J Heise
    Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390 9041, USA
    Methods 40:209-12. 2006
  3. ncbi request reprint Regulation of WNK1 by an autoinhibitory domain and autophosphorylation
    Bing E Xu
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas 75390 9041, USA
    J Biol Chem 277:48456-62. 2002
  4. ncbi request reprint Dimerization in MAP-kinase signaling
    M H Cobb
    Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235 9041, USA
    Trends Biochem Sci 25:7-9. 2000
  5. ncbi request reprint Pharmacological inhibitors of MAPK pathways
    Jessie M English
    1 Dept of Biological Research Oncology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033 2 Dept of Pharmacology, U T Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9041
    Trends Pharmacol Sci 23:40-5. 2002
  6. ncbi request reprint Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2
    Z Chen
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 276:16070-5. 2001
  7. ncbi request reprint Stimulation of NFkappa B activity by multiple signaling pathways requires PAK1
    J A Frost
    Departments of Pharmacology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 275:19693-9. 2000
  8. ncbi request reprint ERK5 and ERK2 cooperate to regulate NF-kappaB and cell transformation
    G Pearson
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA
    J Biol Chem 276:7927-31. 2001
  9. ncbi request reprint MEKK1 binds raf-1 and the ERK2 cascade components
    M Karandikar
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 275:40120-7. 2000
  10. ncbi request reprint Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control
    J M English
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 274:31588-92. 1999

Collaborators

  • Chou Long Huang
  • S Xu
  • J A Frost
  • Z Chen
  • P R Young
  • J A Thomas
  • J C Boehm
  • Z Wang
  • W Chen
  • M Robinson
  • C Shao
  • B Xu
  • P Wu
  • Elizabeth J Goldsmith
  • Zhimin Lu
  • Ying Xia
  • Michael C Lawrence
  • Svetlana Earnest
  • Byung Hoon Lee
  • Malavika Raman
  • G Pearson
  • Angelique W Whitehurst
  • Kathleen McGlynn
  • Charles J Heise
  • Xiaoshan Min
  • Gray W Pearson
  • J M English
  • Julie L Wilsbacher
  • Jessie M English
  • Shih Khoo
  • Fred L Robinson
  • Lingling Duan
  • M Lawrence
  • Steve Stippec
  • Marlon F Levy
  • Bashoo Naziruddin
  • Eunjin Oh
  • M Raman
  • Yingming Zhao
  • Anthony N Anselmo
  • Jian Xie
  • Yu Chi Juang
  • M Karandikar
  • Lisa Y Lenertz
  • M A White
  • K S Berman
  • Tianjun Zhou
  • Angelique Whitehurst
  • Ewen Gallagher
  • M Hutchison
  • Mary Shannon Moore
  • Kate Luby-Phelps
  • Don Arnette
  • Colleen A Vanderbilt
  • Lori B Christerson
  • Chung I Chang
  • Ewen D Gallagher
  • - Xu Be
  • E D Gallagher
  • J L Swantek
  • Jihan Osborne
  • L Duan
  • Elma Zaganjor
  • K McGlynn
  • Arif Jivan
  • Daryl Goad
  • Debbie C Thurmond
  • Kai Zhang
  • Sung Chan Kim
  • Derk Binns
  • A Dang
  • Leonard Craig
  • Andrei V Khokhlatchev
  • A V Khokhlatchev
  • Kyle Wedin
  • Hongjun Shu
  • Michael A White
  • She Chen
  • S Khoo
  • Yan Gao
  • Mischa Machius
  • A Khokhlatchev
  • Tara Beers Gibson
  • Bridgette January
  • Richard J Baer
  • Michael S German
  • Steven C Griffen
  • Paul C Sternweis
  • Youngjai You
  • Clive A Slaughter

Detail Information

Publications72

  1. ncbi request reprint WNK1 activates ERK5 by an MEKK2/3-dependent mechanism
    Bing E Xu
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 279:7826-31. 2004
    ..Finally, ERK5 activation by epidermal growth factor was attenuated by suppression of WNK1 expression using small interfering RNA. Taken together, these results place WNK1 in the ERK5 MAP kinase pathway upstream of MEKK2/3...
  2. ncbi request reprint Expression and characterization of MAP kinases in bacteria
    Charles J Heise
    Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390 9041, USA
    Methods 40:209-12. 2006
    ..The ability to phosphorylate or thiophosphorylate ERK2 in vitro, as described here, is valuable for use in downstream applications designed to investigate MAPK signaling networks...
  3. ncbi request reprint Regulation of WNK1 by an autoinhibitory domain and autophosphorylation
    Bing E Xu
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas 75390 9041, USA
    J Biol Chem 277:48456-62. 2002
    ..We also found that WNK1 expressed in bacteria is autophosphorylated; autophosphorylation on serine 382 in the activation loop is required for its activity...
  4. ncbi request reprint Dimerization in MAP-kinase signaling
    M H Cobb
    Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235 9041, USA
    Trends Biochem Sci 25:7-9. 2000
    ..It is thought that dimerization promotes nuclear localization of ERK2 by its effects on import, export or retention in cytoplasmic and nuclear compartments. Dimerization might also influence substrate interactions...
  5. ncbi request reprint Pharmacological inhibitors of MAPK pathways
    Jessie M English
    1 Dept of Biological Research Oncology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033 2 Dept of Pharmacology, U T Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9041
    Trends Pharmacol Sci 23:40-5. 2002
    ..The results of these efforts have broad implications for the treatment of many diseases...
  6. ncbi request reprint Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2
    Z Chen
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 276:16070-5. 2001
    ..Activation of endogenous TAO2 during differentiation of C2C12 myoblasts paralleled activation of p38 but not JNK/SAPK, consistent with the idea that TAO2 is a physiological regulator of p38 under certain circumstances...
  7. ncbi request reprint Stimulation of NFkappa B activity by multiple signaling pathways requires PAK1
    J A Frost
    Departments of Pharmacology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 275:19693-9. 2000
    ..These data demonstrate that PAK1 is a crucial signaling molecule involved in NFkappaB activation by multiple stimuli...
  8. ncbi request reprint ERK5 and ERK2 cooperate to regulate NF-kappaB and cell transformation
    G Pearson
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA
    J Biol Chem 276:7927-31. 2001
    ..Our results support the hypothesis that NF-kappaB and p90 ribosomal S6 kinase are involved in MEK5-ERK5-dependent focus formation and may serve as integration points for ERK5 and ERK1/2 signaling...
  9. ncbi request reprint MEKK1 binds raf-1 and the ERK2 cascade components
    M Karandikar
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 275:40120-7. 2000
    ..In this study we demonstrate that endogenous MEKK1 binds to endogenous ERK2, MEK1, and another MEKK level kinase, Raf-1, suggesting that it can assemble all three proteins of the ERK2 MAP kinase module...
  10. ncbi request reprint Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control
    J M English
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 274:31588-92. 1999
    ..These observations suggest that ERK5 plays a large role in Raf-1-mediated signal transduction...
  11. pmc Cross-cascade activation of ERKs and ternary complex factors by Rho family proteins
    J A Frost
    U T Southwestern Medical Center, Department of Pharmacology, Dallas 75235 9041, USA
    EMBO J 16:6426-38. 1997
    ..This demonstrates interaction among MAP kinase pathway elements not previously recognized and suggests an explanation for the cooperative effect of Raf-1 and Rho family proteins on cellular transformation...
  12. pmc Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane-associated 195-kDa protein with a large regulatory domain
    S Xu
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75235 9041, USA
    Proc Natl Acad Sci U S A 93:5291-5. 1996
    ....
  13. ncbi request reprint The MEK1 proline-rich insert is required for efficient activation of the mitogen-activated protein kinases ERK1 and ERK2 in mammalian cells
    A Dang
    University of Texas Southwestern Medical Center, Department of Pharmacology, Dallas, Texas 75235 9041, USA
    J Biol Chem 273:19909-13. 1998
    ..We conclude that the proline-rich insert is not the site of the MEK-Raf interaction and that the polyproline insert is required for its efficient activation of downstream ERKs in cells...
  14. ncbi request reprint Identification of substrates and regulators of the mitogen-activated protein kinase ERK5 using chimeric protein kinases
    J M English
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 273:3854-60. 1998
    ..Thus, ERK5 is a target of a novel Ras effector pathway that may communicate with c-Myc...
  15. ncbi request reprint kin-18, a C. elegans protein kinase involved in feeding
    K S Berman
    Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, USA
    Gene 279:137-47. 2001
    ..We have also identified a C. elegans gene that encodes a protein kinase similar to mammalian MAPK/ERK Kinase (MEK) 4 whose promoter is active in the pharynx. It is phosphorylated by TAO1 in vitro and physically interacts with TAO1...
  16. ncbi request reprint MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases
    S Xu
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 272:32056-60. 1997
    ..The data are consistent with a model in which MEKK1-JNK/SAPK binding facilitates the receipt of signals from upstream inputs and localizes JNK/SAPK to intracellular targets of the pathway...
  17. ncbi request reprint Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain
    Z Chen
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 274:28803-7. 1999
    ..These results suggest that TAO proteins lie in stress-sensitive kinase cascades and define a mechanism by which these kinases may organize downstream targets...
  18. ncbi request reprint Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation
    J A Frost
    University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 273:28191-8. 1998
    ..Lamellipodia formation and membrane ruffling caused by active PAK1 expression, however, was independent of PAK1 catalytic activity and likely requires interaction among multiple proteins binding to the PAK1 regulatory domain...
  19. ncbi request reprint Reconstitution of mitogen-activated protein kinase phosphorylation cascades in bacteria. Efficient synthesis of active protein kinases
    A Khokhlatchev
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 272:11057-62. 1997
    ..6-2.3 micromol/min/mg. Coexpression of protein kinases with their substrates in bacteria is of great value in the preparation of numerous phosphoproteins, heretofore not possible in procaryotic expression systems...
  20. pmc Activation of mitogen-activating protein kinase by glucose is not required for insulin secretion
    S Khoo
    University of Texas Southwestern Medical Center, Department of Pharmacology, 5323 Harry Hines Boulevard, Dallas, TX 75235 9041, USA
    Proc Natl Acad Sci U S A 94:5599-604. 1997
    ..These findings suggest that some of the glucose-dependent actions of ERKs will be exerted in the nucleus...
  21. ncbi request reprint Uncoupling Raf1 from MEK1/2 impairs only a subset of cellular responses to Raf activation
    G Pearson
    Departments of Cell Biology and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 275:37303-6. 2000
    ..In addition, Raf-dependent activation of p90 ribosomal S6 kinase was only slightly impaired. These results support the hypothesis that Raf kinases utilize multiple downstream effectors to regulate distinct cellular activities...
  22. ncbi request reprint Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking
    - Xu Be
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 276:26509-15. 2001
    ..These findings suggest complex interactions of MEK1 D domains with ERK2 that influence its activation and its effects on substrates...
  23. ncbi request reprint WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II
    B Xu
    Departments of Pharmacology and Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 275:16795-801. 2000
    ..This distinct organization of catalytic residues indicates that WNK1 belongs to a novel family of serine/threonine protein kinases...
  24. pmc MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of mitogen-activated protein kinase
    S Xu
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235 9041, USA
    Proc Natl Acad Sci U S A 92:6808-12. 1995
    ..Thus, other as yet undefined mechanisms may be involved in determining information flow through the MAP kinase and related pathways...
  25. ncbi request reprint The N-terminal ERK-binding site of MEK1 is required for efficient feedback phosphorylation by ERK2 in vitro and ERK activation in vivo
    B e Xu
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 274:34029-35. 1999
    ..Using ERK2-p38 chimeras and an ERK2 deletion mutant, a MEK1-binding site of ERK2 was localized to its N terminus...
  26. ncbi request reprint ERKs weigh in on ribosome mass
    E D Gallagher
    Department of Pharmacology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 8:932-3. 2001
    ..This provides a connection between growth factor signaling and increased translation...
  27. doi request reprint The protein kinases ERK1/2 and their roles in pancreatic beta cells
    M Lawrence
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9041, USA
    Acta Physiol (Oxf) 192:11-7. 2008
    ....
  28. ncbi request reprint Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation
    A V Khokhlatchev
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas 75235 9041, USA
    Cell 93:605-15. 1998
    ..Other MAP kinase family members also form dimers. The generality of this behavior suggests that dimerization is part of the mechanism of action of the MAP kinase family...
  29. ncbi request reprint Structural basis of inhibitor selectivity in MAP kinases
    Z Wang
    Department of Biochemistry The University of Texas Southwestern Medical Center at Dallas 5323 Harry Hines Boulevard, Dallas, TX 75235, USA
    Structure 6:1117-28. 1998
    ..Although these compounds are known to bind to the ATP-binding site, the origin of the inhibitory specificity toward p38 is not clear...
  30. ncbi request reprint ERK3 is a constitutively nuclear protein kinase
    M Cheng
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75235 9041, USA
    J Biol Chem 271:8951-8. 1996
    ..Despite marked similarities to ERK1 and ERK2, ERK3 does not phosphorylate typical MAP kinase substrates, indicating that it has distinct functions...
  31. ncbi request reprint How MAP kinases are regulated
    M H Cobb
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235 9041, USA
    J Biol Chem 270:14843-6. 1995
  32. ncbi request reprint Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades
    M Hutchison
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9041, USA
    J Biol Chem 273:28625-32. 1998
    ..The activation of and binding to MEK3 by TAO1 implicates TAO1 in the regulation of the p38-containing stress-responsive MAP kinase pathway...
  33. ncbi request reprint Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions
    G Pearson
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Endocr Rev 22:153-83. 2001
    ..This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2...
  34. ncbi request reprint IL-1 receptor-associated kinase modulates host responsiveness to endotoxin
    J L Swantek
    Departments of Pharmacology, Pediatrics, and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA
    J Immunol 164:4301-6. 2000
    ..These findings, coupled with the critical role for IRAK in IL-1 and IL-18 signal transduction, demonstrate the importance of this kinase and the IL-1/Toll signaling cassette in sensing and responding to Gram-negative infection...
  35. ncbi request reprint Mitogen-activated protein kinase pathways
    M J Robinson
    University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 904, 1 USA
    Curr Opin Cell Biol 9:180-6. 1997
    ....
  36. ncbi request reprint Isolation of MEK5 and differential expression of alternatively spliced forms
    J M English
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235 9041, USA
    J Biol Chem 270:28897-902. 1995
    ....
  37. ncbi request reprint Differential regulation and properties of MAPKs
    M Raman
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
    Oncogene 26:3100-12. 2007
    ..Here, we describe some of the properties of the three major MAPK pathways and discuss how these properties govern pathway regulation and activity...
  38. ncbi request reprint The death effector domain protein PEA-15 prevents nuclear entry of ERK2 by inhibiting required interactions
    Angelique W Whitehurst
    Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9041, USA
    J Biol Chem 279:12840-7. 2004
    ..These results suggest that PEA-15 sequesters ERK2 in the cytoplasm at least in part by interfering with its ability to interact with nucleoporins, presenting a potential paradigm for regulation of ERK2 localization...
  39. ncbi request reprint Structure of MAPKs
    Elizabeth J Goldsmith
    Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
    Methods Mol Biol 250:127-44. 2004
  40. pmc Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in beta-cells
    Michael C Lawrence
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 105:13315-20. 2008
    ..These findings imply that MAPK-containing signaling complexes are positioned on sensitive promoters with their protein substrates to modulate transcription in situ in response to incoming signals...
  41. ncbi request reprint TAO (thousand-and-one amino acid) protein kinases mediate signaling from carbachol to p38 mitogen-activated protein kinase and ternary complex factors
    Zhu Chen
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 278:22278-83. 2003
    ..Taken together, these studies suggest that TAO protein kinases relay signals from carbachol through heterotrimeric G proteins to the p38 MAP kinase, which then activates TCFs in the nucleus...
  42. ncbi request reprint Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1
    Fred L Robinson
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 277:14844-52. 2002
    ..These data suggest an essential role for the MAP kinase insert and residues within or just preceding alpha-helix G in the interaction of ERK2 with MEK1/2...
  43. ncbi request reprint Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b
    Chung I Chang
    Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 9:1241-9. 2002
    ..The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip...
  44. ncbi request reprint Cell condition-dependent regulation of ERK5 by cAMP
    Gray W Pearson
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75390 9041, USA
    J Biol Chem 277:48094-8. 2002
    ..Our results suggest that regulation of MAP kinase pathways by cAMP is not only dictated by cell type, but also by cell context...
  45. ncbi request reprint WNK1 activates SGK1 by a phosphatidylinositol 3-kinase-dependent and non-catalytic mechanism
    Bing E Xu
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 280:34218-23. 2005
    ..Phosphorylation of WNK1 on Thr-58 contributes to SGK1 activation. Finally, we show that WNK1 is required for the activation of SGK1 by insulin-like growth factor 1...
  46. pmc Cyclic AMP selectively uncouples mitogen-activated protein kinase cascades from activating signals
    Gray W Pearson
    Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390 9041, USA
    Mol Cell Biol 26:3039-47. 2006
    ..Collectively, these results support a model in which cAMP shapes the growth factor-induced cellular response through PKA-dependent uncoupling of selected MAP kinase cascades from activating signals...
  47. ncbi request reprint Role of with-no-lysine [K] kinases in the pathogenesis of Gordon's syndrome
    Jian Xie
    Department of Medicine, Room J5 104, MC 8856, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390 8856, USA
    Pediatr Nephrol 21:1231-6. 2006
    ..Here, we review the pathogenesis of PHA II based on current understanding of the actions of WNK1 and WNK4 on Na+ and K+ handling in the renal distal tubule...
  48. pmc WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells
    Anthony N Anselmo
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 103:10883-8. 2006
    ..OSR1 and SPAK are likely links between WNK1 and NKCC in a pathway that contributes to volume regulation and blood pressure homeostasis in mammals...
  49. ncbi request reprint Characterization of mitogen-activated protein kinase (MAPK) dimers
    Julie L Wilsbacher
    Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390 9041, USA
    Biochemistry 45:13175-82. 2006
    ....
  50. ncbi request reprint Biological cross-talk between WNK1 and the transforming growth factor beta-Smad signaling pathway
    Byung Hoon Lee
    Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9041, USA
    J Biol Chem 282:17985-96. 2007
    ..In addition, TGFbeta-induced target gene transcripts were increased in WNK1 small interfering RNA cells. These findings suggest WNK1 as a dual modulator of TGFbeta-Smad signaling pathways...
  51. pmc TAO kinases mediate activation of p38 in response to DNA damage
    Malavika Raman
    Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, TX 75390 9041, USA
    EMBO J 26:2005-14. 2007
    ..These findings indicate that TAO kinases are regulators of p38-mediated responses to DNA damage and are intermediates in the activation of p38 by ATM...
  52. pmc Differential regulation of CHOP-10/GADD153 gene expression by MAPK signaling in pancreatic beta-cells
    Michael C Lawrence
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 104:11518-25. 2007
    ..These results indicate that ERK1/2 have dual roles in regulating CHOP gene expression via both promoter and intronic regions, depending on environmental and metabolic stresses imposed on pancreatic beta-cells...
  53. pmc WNK1 is a novel regulator of Munc18c-syntaxin 4 complex formation in soluble NSF attachment protein receptor (SNARE)-mediated vesicle exocytosis
    Eunjin Oh
    Department of Biochemistry and Molecular Biology, Center for Diabetes Research, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA
    J Biol Chem 282:32613-22. 2007
    ..Taken together, these data support a novel role for WNK1 and a new mechanism for the regulation of SNARE complex assembly by WNK1-Munc18c complexes...
  54. ncbi request reprint WNKs: protein kinases with a unique kinase domain
    Chou Long Huang
    Department of Medicine, University of Texas, Southwestern Medical Center, Dallas, Texas 75390, USA
    Exp Mol Med 39:565-73. 2007
    ..Here, we review roles of WNK kinases in the regulation of ion balance, cell signaling, survival, and proliferation, and embryonic organ development...
  55. ncbi request reprint Different domains of the mitogen-activated protein kinases ERK3 and ERK2 direct subcellular localization and upstream specificity in vivo
    Megan J Robinson
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 277:5094-100. 2002
    ....
  56. doi request reprint The roles of MAPKs in disease
    Michael C Lawrence
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390 9041, USA
    Cell Res 18:436-42. 2008
    ..Disturbances in this and other regulatory pathways may result in the contribution of ERK1/2 to the etiology of certain human disorders...
  57. pmc WNK1 activates SGK1 to regulate the epithelial sodium channel
    Bing E Xu
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9041, USA
    Proc Natl Acad Sci U S A 102:10315-20. 2005
    ..This finding provides compelling evidence that this molecular mechanism contributes to the pathogenesis of hypertension in pseudohypoaldosteronism type II caused by WNK1 and, possibly, in other forms of hypertension...
  58. ncbi request reprint Properties of WNK1 and implications for other family members
    Lisa Y Lenertz
    Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Biol Chem 280:26653-8. 2005
    ..However, WNK1 phosphorylated both WNK4 and WNK2. In addition, the WNK1 autoinhibitory domain inhibited the catalytic activity of these WNKs. These findings suggest potential mechanisms for interconnected regulation of WNK family members...
  59. ncbi request reprint Stimulus-specific requirements for MAP3 kinases in activating the JNK pathway
    Wei Chen
    Departments of Pharmacology and Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9041, USA
    J Biol Chem 277:49105-10. 2002
    ..On the other hand, sorbitol requires expression of four MAP3Ks to cause maximal JNK activation. Thus, we demonstrate that specific stimuli use different mechanisms to recruit distinct MAP3Ks to regulate the JNK pathway...
  60. ncbi request reprint Binding of JNK/SAPK to MEKK1 is regulated by phosphorylation
    Ewen D Gallagher
    University of Texas Southwestern Medical Center, Department of Pharmacology, Dallas, Texas 75390 9041, USA
    J Biol Chem 277:45785-92. 2002
    ..Phosphorylation of this site inhibits binding of JNK/SAPK to MEKK1. Thus, we propose a mechanism by which the MEKK1-dependent JNK/SAPK pathway is negatively regulated by PAK through phosphorylation of serine 67...
  61. ncbi request reprint Regulation of ERK1 and ERK2 by glucose and peptide hormones in pancreatic beta cells
    Don Arnette
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 278:32517-25. 2003
    ..The glucose-sensitive mechanism is distinct from that used by phorbol ester or insulin to stimulate ERK1/2 but shares common features with that used by GLP-1...
  62. ncbi request reprint Regulation of insulin gene transcription by ERK1 and ERK2 in pancreatic beta cells
    Shih Khoo
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 278:32969-77. 2003
    ..Phosphorylation increases their functional activity and results in a cumulative transactivation of the promoter. Thus, ERK1/2 act at multiple points to transduce a glucose signal to insulin gene transcription...
  63. ncbi request reprint MAP kinase modules: many roads home
    Malavika Raman
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulvard, Dallas, TX 75390 9041, USA
    Curr Biol 13:R886-8. 2003
  64. ncbi request reprint p115 Rho GTPase activating protein interacts with MEKK1
    Lori B Christerson
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Cell Physiol 192:200-8. 2002
    ..Here we have identified an MEKK1 binding partner that offers a connection between this protein kinase and the machinery regulating cytoskeletal reorganization...
  65. ncbi request reprint Characterization of OSR1, a member of the mammalian Ste20p/germinal center kinase subfamily
    Wei Chen
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 279:11129-36. 2004
    ..Replacement of threonine 84 with glutamate reduced the activation of PAK1 by an active form of the small G protein Cdc42, suggesting that phosphorylation by OSR1 modulates the G protein sensitivity of PAK isoforms...
  66. ncbi request reprint The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2
    Zhimin Lu
    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 9:945-56. 2002
    ..Therefore, MEKK1 functions not only as an upstream activator of the ERK and JNK through its kinase domain, but also as an E3 ligase through its PHD domain, providing a negative regulatory mechanism for decreasing ERK1/2 activity...
  67. ncbi request reprint Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension
    Xiaoshan Min
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Structure 12:1303-11. 2004
    ..The structure of the WNK1 catalytic domain, with its unique active site, may help in the design of therapeutic reagents for the treatment of hypertension...
  68. ncbi request reprint WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding
    Byung Hoon Lee
    Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 15:741-51. 2004
    ..These findings provide a biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. Interruption of this regulatory pathway may disturb membrane events that regulate ion balance...
  69. ncbi request reprint Crystal structure of the TAO2 kinase domain: activation and specificity of a Ste20p MAP3K
    Tianjun Zhou
    Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Structure 12:1891-900. 2004
    ..Finally, active TAO2 displays unusual interactions with ATP, involving, in part, a subgroup-specific C-terminal extension of TAO2. The observed interactions may be useful in making specific inhibitors of TAO kinases...
  70. pmc ERK2 enters the nucleus by a carrier-independent mechanism
    Angelique W Whitehurst
    Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9041, USA
    Proc Natl Acad Sci U S A 99:7496-501. 2002
    ..Our data suggest that GFP-ERK2 enters the nucleus by a saturable, facilitated mechanism, distinct from a carrier- and energy-dependent import mechanism and involves a direct interaction with nuclear pore complex proteins...
  71. ncbi request reprint WNK1: analysis of protein kinase structure, downstream targets, and potential roles in hypertension
    Bing E Xu
    Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, USA
    Cell Res 15:6-10. 2005
    ..The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function...
  72. pmc Stimulus-coupled spatial restriction of extracellular signal-regulated kinase 1/2 activity contributes to the specificity of signal-response pathways
    Angelique Whitehurst
    Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
    Mol Cell Biol 24:10145-50. 2004
    ..Therefore, nuclear accumulation of active ERK1/2 is a discrete regulated step that can direct the function of the kinase in response to specific stimuli...