Joe Ramos, Ph.D.

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Cancer Research Center of Hawaii

Joe W. Ramos, Ph.D.
Assistant Professor (Researcher), Cancer Research Center of Hawaii;
Adjunct Associate Professor of Cell Biology, John A. Burns School of Medicine;
Graduate Faculty, Cell and Molecular Biology and Molecular Biosciences and Bioengineering
Ph.D. (Cell Biology), University of Virginia
jramos@crch.hawaii.edu

Visit the Ramos Lab website

Publication list via Pubmed
Cell-signaling, integrins, cell adhesion, cancer
Our mission is to understand the regulation of the MAP kinase pathway. In particular, we have focused on how activation of this ubiquitous pathway can give rise to different outcomes in different cells. As a first step in this work, we used expression cloning to isolate proteins that interfere with ERK MAP kinase signaling to the cell adhesion proteins the integrins. One such protein is PEA-15. PEA-15 can alter ERK signaling to other proteins as well, including the transcription factor Elk1 and the kinase Rsk2.
PEA-15 is widely expressed throughout the body, with particularly high levels expressed in astrocytes and lymphocytes. The structure of PEA-15 is striking in that the N-terminal half of the protein consists of a conserved death effector domain. This domain is usually found in proteins involved in apoptosis. Indeed, PEA-15 prevents FADD-mediated apoptosis. The C-terminal half of the protein contains two phosphorylated serines that appear to regulate PEA-15 function. Our work has shown that PEA-15 binds directly to ERK and maintains it in the cytoplasm. Similarly PEA-15 can also bind to Rsk2 and may therefore affect ERK activation of Rsk2 in the cytoplasm. By determining the location in the cell of these kinases PEA-15 can channel ERK signaling to cytoplasmic substrates to the exclusion of nuclear targets like the transcription factor ELK1 and thus modify the outcome of ERK activation.
We are using PEA-15 null mice and molecular and cell biological approaches to better understand the function of PEA-15. We have also begun to isolate and characterize related proteins. Because of the fundamental nature of this work it has applications to a number of pathological states including cancer and diabetes.

Active Grants
J.W. Ramos, Principal Investigator
R01-CA93849
“Regulation of Cell Signaling and Adhesion"
2002-2008

J.W. Ramos
Congressional Special Interest (CSI), Department of Defense (DOD), Medical Research Material Command (MRMC)
“Collaborative Cancer Research Program Between Tripler Army Medical Center and the Cancer Research Center of Hawai‘i(CRCH)"
2006-2009

Selected Publications
J.W. Ramos. (2008). The Regulation of Extracellular Signal-Regulated Kinase (ERK) in Mammalian Cells. IJBCB, 40(12):2707-2719.

H. Vaidyanathan, J. Opoku-Ansah, S. Pastorino, H. Renganathan, M.L. Matter and J.W. Ramos. (2007). ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. PNAS, 105(50):19837-19842.

F. Renault-Mihara, F. Beuvon, X. Iturrioz, B. Canton, S. De Bouard, N. Léonard, S. Mouhamad, A. Sharif, J.W. Ramos, M-P. Junier, and H Chneiweiss. (2006). PEA-15 Expression Inhibits Astrocyte Migration by a PKC Delta-Dependent Mechanism. Mol. Biol. Cell, 17(12):5141-52.

H. Renganathan, H. Vaidyanathan, A. Knapinska and J.W. Ramos. (2005). Phosphorylation of PEA-15 Switches its Binding Specificity from ERK MAP kinase to FADD. Biochem J., 390(3):729-735.

H. Vaidyanathan and J.W. Ramos. (2003). Rsk2 activity is regulated by its association with PEA-15. J. Biol. Chem. 278(34):32367-32372.

J.W. Ramos*, E. Formstecher*, M. Fauquet, D.A. Calderwood, J-C. Hsieh, B. Canton, X-T. Nguyen, J-V. Barnier, J. Camonis, M.H. Ginsberg, and H. Chneiweiss. (2001). PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase. Developmental Cell 1:239-250. *Co-first authors.

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