Research Topics
Genomes and Genes
| M J WeberSummaryAffiliation: University of Virginia Country: USA Publications
Research Grants
| Collaborators
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Detail Information
Publications
Ras signaling in prostate cancer progressionMichael J Weber
Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, Virginia 22908, USA
J Cell Biochem 91:13-25. 2004..g., phosphorylations) of transcriptional cofactors might be responsible for modulating the function of the AR so that it is active even at low concentrations of androgen...- Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogsScott T Eblen
Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
J Biol Chem 278:14926-35. 2003..These results not only identify two novel ERK2 substrates but also provide a framework for the future identification of numerous cellular targets of this important signaling cascade... - Src phosphorylates the insulin-like growth factor type I receptor on the autophosphorylation sites. Requirement for transformation by srcJ E Peterson
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
J Biol Chem 271:31562-71. 1996..Thus, the Src kinase can substitute for the receptor kinase in phosphorylating and activating the IGF-I receptor, and this receptor phosphorylation and activation are essential for transformation by src... - MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascadeH J Schaeffer
Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
Science 281:1668-71. 1998..Expression of MP1 in cells increased binding of ERK1 to MEK1. MP1 apparently functions as an adapter to enhance the efficiency of the MAP kinase cascade... - Identifying specific kinase substrates through engineered kinases and ATP analogsN Vinay Kumar
Department of Microbiology and Cancer Center, University of Virginia, Health Science Center, Charlottesville, VA 22908, USA
Methods 32:389-97. 2004..We also describe the direct labeling of ERK2 substrates in cell lysates. These methodologies can be adapted for use with other protein kinases to increase the understanding of intracellular signal transduction... - Biochemical analysis of MEK activation in NIH3T3 fibroblasts. Identification of B-Raf and other activatorsC W Reuter
Department of Microbiology, University of Virginia Health Sciences Center, School of Medicine, Charlottesville 22908, USA
J Biol Chem 270:7644-55. 1995..These data provide direct evidence that 93-95-kDa B-Raf isozymes and an unidentified 40-50-kDa MEK activator are major agonist-specific MEK activators in NIH3T3 fibroblasts... 
RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2T Jelinek
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville 22908
Mol Cell Biol 14:8212-8. 1994....- PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activationJill K Slack-Davis
Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA
J Cell Biol 162:281-91. 2003.... - Restoration of PTEN expression alters the sensitivity of prostate cancer cells to EGFR inhibitorsZ Wu
Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA
Prostate 68:935-44. 2008..Although there are data implicating PI3K-Akt or MAPK pathway activation with resistance to EGFR inhibitors in CaP, the potential cross-talk between these pathways in response to EGFR or MAPK inhibitors remains to be examined... - Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective mannerD H Nguyen
Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
J Cell Biol 146:149-64. 1999..Thus, we have demonstrated that uPA promotes cellular migration, in an integrin-selective manner, by initiating a uPAR-dependent signaling cascade in which Ras, MEK, ERK, and MLCK serve as essential downstream effectors... - Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sitesDaniel Gioeli
Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
J Biol Chem 277:29304-14. 2002..These data provide a basis for analyzing mechanisms of cross-talk between growth factor signaling and androgen in prostate development, physiology, and cancer... - Active MAP kinase in mitosis: localization at kinetochores and association with the motor protein CENP-EM Zecevic
Department of Microbiology and Cancer Center, University of Virginia, Health Sciences Center, Charlottesville, Virginia 22908, USA
J Cell Biol 142:1547-58. 1998.... - Tumor necrosis factor alpha induces BID cleavage and bypasses antiapoptotic signals in prostate cancer LNCaP cellsG Kulik
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
Cancer Res 61:2713-9. 2001..The ability of TNF-alpha to bypass survival signals from activated EGF receptor and Akt in prostate cancer cells makes death receptor signaling a promising avenue for therapeutic intervention... - Akt-dependent and -independent survival signaling pathways utilized by insulin-like growth factor IG Kulik
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
Mol Cell Biol 18:6711-8. 1998..These findings demonstrate the existence of a new survival signaling pathway independent of PI3 kinase, Akt, and new transcription and which is evident in fibroblasts overexpressing the IGF-I receptor... - Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cellsZ Wu
Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
Prostate 66:1114-23. 2006..While the transcriptional activity of the androgen receptor (AR) is inhibited by PTEN in androgen sensitive prostate cancer (CaP), the role of PTEN in androgen disease is unclear... - Attenuation of Ras signaling restores androgen sensitivity to hormone-refractory C4-2 prostate cancer cellsRobert E Bakin
Department of Microbiology, Cancer Center and Paul Mellon Prostate Cancer Institute, Charlottesville, Virginia 22908, USA
Cancer Res 63:1975-80. 2003.... - Constitutive activation of the Ras/mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cellsRobert E Bakin
Department of Microbiology and Cancer Center and Paul Mellon Prostate Cancer Research Institute, University of Virginia, Charlottesville, Virginia 22908, USA
Cancer Res 63:1981-9. 2003..This provides a common mechanism for prostate cancer progression driven by diverse agonists... - Tyrosine kinases are required for catecholamine secretion and mitogen-activated protein kinase activation in bovine adrenal chromaffin cellsM E Cox
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA
J Neurochem 66:1103-12. 1996..These results demonstrate that an unidentified Ca(2+)-activated tyrosine kinase(s) is required for MAPK activation and exocytosis in chromaffin cells and suggest that MAPK participates in the regulation of secretion... - Smac is required for cytochrome c-induced apoptosis in prostate cancer LNCaP cellsJonathan P Carson
Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA
Cancer Res 62:18-23. 2002..These results further emphasize the central role of mitochondria in the regulation of apoptosis in prostate cancer cells... - Sequence of pp42/MAP kinase, a serine/threonine kinase regulated by tyrosine phosphorylationJ H Her
Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville 22908
Nucleic Acids Res 19:3743. 1991 - Subcellular localization modulates activation function 1 domain phosphorylation in the androgen receptorCristina T Kesler
Center for Cell Signaling, Department of Microbiology, University of Virginia Health System, Charlottesville, Virginia 22908, USA
Mol Endocrinol 21:2071-84. 2007..We propose that one function of nucleocytoplasmic shuttling is to integrate the signaling environment in the cytoplasm with AR activity in the nucleus... - Receptor for activated C kinase 1 (RACK1) and Src regulate the tyrosine phosphorylation and function of the androgen receptorSarah Kraus
Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, Virginia, USA
Cancer Res 66:11047-54. 2006..Our results suggest that RACK1 mediates the cross-talk of AR with additional binding partners, such as Src, and facilitates the tyrosine phosphorylation and transcriptional activity of the AR... - The neuroendocrine-derived peptide parathyroid hormone-related protein promotes prostate cancer cell growth by stabilizing the androgen receptorJohn DaSilva
Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, Virginia 22908 0734, USA
Cancer Res 69:7402-11. 2009..These events result in increased accumulation of AR and thus enhanced growth of prostate cancer cells at low levels of androgen... - A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK functionA D Catling
Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville 22908, USA
Mol Cell Biol 15:5214-25. 1995..These observations indicate a critical role for the PR sequence in directing specific protein-protein interactions important for the activation, inactivation, and downstream functioning of the MEKs... - The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferationD E Clark
Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA
Cancer Res 65:3108-16. 2005..These results suggest that proliferation of some prostate cancer cells is dependent on RSK activity and support the hypothesis that RSK may be an important chemotherapeutic target for prostate cancer... - In situ visualization of intratumor growth factor signaling: immunohistochemical localization of activated ERK/MAP kinase in glial neoplasmsJ W Mandell
Department of Pathology Neuropathology, University of Virginia School of Medicine, Charlottesville 22908, USA
Am J Pathol 153:1411-23. 1998..Although ERK/MAPK activation was not restricted to neoplastic glia, consistent patterns of selective activation in tumor cells suggests that sustained activation may contribute to the neoplastic glial phenotype... - Transient, ligand-dependent arrest of the androgen receptor in subnuclear foci alters phosphorylation and coactivator interactionsBen E Black
Center for Cell Signaling, Department of Biochemistry and Molecular Genetics, Box 800577 Health Systems, University of Virginia, Charlottesville, VA 22908, USA
Mol Endocrinol 18:834-50. 2004..Our working model is that the subnuclear foci are sites where AR undergoes ligand-dependent engagement with GRIP-1 and CBP, a recruitment step that occurs before Ser81 phosphorylation and association with promoters of target genes... - Rap2 regulates androgen sensitivity in human prostate cancer cellsDora Bigler
Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
Prostate 67:1590-9. 2007..Here we ask if Rap proteins play a role in determining androgen sensitivity of human prostate cancer cells either alone or in the context of an activated Ras... - Rac-PAK signaling stimulates extracellular signal-regulated kinase (ERK) activation by regulating formation of MEK1-ERK complexesScott T Eblen
Department of Microbiology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA
Mol Cell Biol 22:6023-33. 2002..These findings reveal a novel mechanism by which adhesion and growth factor signals are integrated during ERK activation... - Raffling off the effectors of RasMichael J Weber
Univ. of Virginia School of Medicine; 2-16 Jordan Hall; Charlottesville, Virginia 22908 USA
Cancer Biol Ther 2:76-7. 2003 - Stress kinase signaling regulates androgen receptor phosphorylation, transcription, and localizationDaniel Gioeli
Department of Microbiology, P O Box 800734, University of Virginia Health System, Charlottesville, Virginia 22908, USA
Mol Endocrinol 20:503-15. 2006..Our data suggest that stress kinase signaling and nuclear export regulate AR transcriptional activity... - MEK partner 1 (MP1): regulation of oligomerization in MAP kinase signalingCharu Sharma
Department of Microbiology and Cancer Center, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA
J Cell Biochem 94:708-19. 2005..These results support the concept that MP1 functions as a regulator of MAP kinase signaling by binding to MEK1 and regulating its association with a larger signaling complex that may sequentially service multiple molecules of ERK... - Mitogen-activated protein kinase feedback phosphorylation regulates MEK1 complex formation and activation during cellular adhesionScott T Eblen
Department of Microbiology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA
Mol Cell Biol 24:2308-17. 2004..We propose that activation of ERK during adhesion creates a feedback system in which ERK phosphorylates MEK1 on T292, and this in turn blocks additional S298 phosphorylation in response to integrin signaling... - Identification of Tyr-185 as the site of tyrosine autophosphorylation of recombinant mitogen-activated protein kinase p42mapkA J Rossomando
Department of Microbiology, University of Virginia, Charlottesville, VA 22908
Proc Natl Acad Sci U S A 89:5779-83. 1992..Mass spectrometry and phosphopeptide mapping showed that tyrosine phosphorylation of recombinant p42mapk occurs on Tyr-185, the site of regulatory tyrosine phosphorylation that occurs in mitogen-stimulated mammalian cells... - RACK1 targets the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to link integrin engagement with focal adhesion disassembly and cell motilityTomas Vomastek
Department of Microbiology and Cancer Center, University of Virginia Health Science Center, Charlottesville, VA 22908, USA
Mol Cell Biol 27:8296-305. 2007..We suggest that RACK1 tethers the ERK pathway core kinases and channels signals from upstream activation by integrins to downstream targets at focal adhesions... - Modular construction of a signaling scaffold: MORG1 interacts with components of the ERK cascade and links ERK signaling to specific agonistsTomas Vomastek
Department of Microbiology and Cancer Center, University of Virginia, Charlottesville, VA 22908, USA
Proc Natl Acad Sci U S A 101:6981-6. 2004..We propose that MORG1 is a component of a modular scaffold system that participates in the regulation of agonist-specific ERK signaling... - The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activityMaofu Fu
Department of Oncology, Georgetown University Medical Center, Washington, D C 20057, USA
J Biol Chem 279:29436-49. 2004..Together these studies suggest that acetylation and phosphorylation of the AR are linked events and that the conserved AR lysine motif contributes to a select subset of pathways governing AR activity... - Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylationKonduru S R Sastry
Department of Cancer Biology, Section on Comparative Medicine, and Center for Human Genomics, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
J Biol Chem 282:14094-100. 2007..Antiapoptotic signaling by epinephrine could be one of the mechanisms by which stress promotes tumorigenesis and decreases the efficacy of anti-cancer therapies... - Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interactionTomas Vomastek
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India
Mol Cell Biol 28:6954-66. 2008..We propose that Tpr is both a substrate and a scaffold for activated ERKs... 
The current state of preclinical prostate cancer animal modelsKenneth J Pienta
University of Michigan, Department of Internal Medicine, Ann Arbor, MI, USA
Prostate 68:629-39. 2008..It should be possible to apply the knowledge gained molecular and epigenetic studies to develop new cell lines and models that mimic progressive and fatal prostate cancer and ultimately improve interventions...
Research Grants
- Androgen and Growth Factor Signaling in Prostate CancerMichael Weber; Fiscal Year: 2007..This research will be informative with respect to understanding the integration of steroid and growth factor signaling, as well as in identifying the optimal therapeutic targets for advanced prostate cancer. ..
- SIGNAL TRANSDUCTION BY TYROSINE KINASESMichael Weber; Fiscal Year: 2001..These investigations will assess a) the role of PI 3-kinase b) the regulation of stress kinases, c) the participation of the bcl-2 family in IGF-I receptor signaling, and d) the role of a newly identified MEK activator. ..