Abstract

This is a first amended renewal of a grant, currently in its fifth year, to study the regulation and function of p42 MAP kinase. The MAP kinases are crucial components of diverse signalling cascades. In general, Dr. Weber is testing the hypothesis that specific protein:protein interactions control the upstream regulators and downstream effectors of MAP kinase cascades as well as the timing of MAP kinase activation and the cellular location of components of the cascades. The project is divided into three specific aims. In the first aim he will examine how interactions with specific MEK activators and scaffolding proteins can regulate the efficiency with which ERKs are activated and the cross-talk with other MAP kinase family members.
In Aim 2 he will determine how activation of ERKs can occur during mitosis and how activation at this time in the cell cycle provides MAP kinase with a new repertoire of possible functions.
In Aim 3 he will test the idea that interaction of ERKs with transcription factors regulates the translocation of ERKs to the nucleus and thus controls their ability to participate in the regulation of gene expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047332-07
Application #
2838588
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1992-05-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Virginia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Vomastek, Tomas; Schaeffer, Hans-Joerg; Tarcsafalvi, Adel et al. (2004) Modular construction of a signaling scaffold: MORG1 interacts with components of the ERK cascade and links ERK signaling to specific agonists. Proc Natl Acad Sci U S A 101:6981-6
Eblen, Scott T; Slack, Jill K; Weber, Michael J et al. (2002) Rac-PAK signaling stimulates extracellular signal-regulated kinase (ERK) activation by regulating formation of MEK1-ERK complexes. Mol Cell Biol 22:6023-33
Gioeli, D; Zecevic, M; Weber, M J (2001) Immunostaining for activated extracellular signal-regulated kinases in cells and tissues. Methods Enzymol 332:343-53
Eblen, S T; Catling, A D; Assanah, M C et al. (2001) Biochemical and biological functions of the N-terminal, noncatalytic domain of extracellular signal-regulated kinase 2. Mol Cell Biol 21:249-59
Carson, J P; Kulik, G; Weber, M J (1999) Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3'-kinase and Akt/protein kinase B. Cancer Res 59:1449-53
Gao, Z; Chen, T; Weber, M J et al. (1999) A2B adenosine and P2Y2 receptors stimulate mitogen-activated protein kinase in human embryonic kidney-293 cells. cross-talk between cyclic AMP and protein kinase c pathways. J Biol Chem 274:5972-80
Schaeffer, H J; Weber, M J (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 19:2435-44
Chen, T; Cho, R W; Stork, P J et al. (1999) Elevation of cyclic adenosine 3',5'-monophosphate potentiates activation of mitogen-activated protein kinase by growth factors in LNCaP prostate cancer cells. Cancer Res 59:213-8
Gioeli, D; Mandell, J W; Petroni, G R et al. (1999) Activation of mitogen-activated protein kinase associated with prostate cancer progression. Cancer Res 59:279-84
Schaeffer, H J; Catling, A D; Eblen, S T et al. (1998) MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. Science 281:1668-71

Showing the most recent 10 out of 29 publications