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Department of Anatomy

Roose Laboratory | University of California, San Francisco | Department of Anatomy | 513 Parnassus Avenue HSW 1330 | San Francisco CA 94143-0452


Abel SM, Roose JP, Groves JT, Weiss A, Chakraborty AK.

The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks.

J Phys Chem B. 2012 Mar 13.


Evan Markegard, Evan Trager, Chih-wen Ou Yang, Weiguo Zhang, Arthur Weiss, and Jeroen P. Roose.

Basal LAT-diacylglycerol-RasGRP1 Signals in T cells Maintain TCR-alpha Gene Expression.

PLoS ONE, 2011;6(9):e25540. Epub 2011 Sep 26.

Andre Limnander, Philippe Depeille, Jen Liou, Michael Leitges, Tomohiro Kurosaki, Jeroen P. Roose and Arthur Weiss.

Stim1, PKCdelta and RasGRP Proteins Set a Threshold for Pro-Apoptotic Erk Signaling During B cell Development.

Nature Immunology, 2011 May;12(5):425-33.



Jennifer O. Lauchle, Doris Ki, Doan T. Le, Keiko Akagi, Michael Crone, Kimberly Krisman, Kegan Warner, Jeannette M. Bonifas, Qing Li, Kristin M. Coakley, Ernesto Diaz-Flores, Matthew Gorman, Sally Przybranowski, Mary Tran, Scott C. Kogan, Jeroen P. Roose, Neal Copeland, Nancy Jenkins, Luis Parada, Linda Wolff, Judith Sebolt-Leopold, and Kevin Shannon.

Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras.

Nature. 2009 Sep 17;461(7262):411-4.


Jayajit Das, Mary Ho, Julie Zikherman, Christopher Gover, Ming Yang, Arthur Weiss, Arup K. Chakraborty, and Jeroen P. Roose.

Digital signaling and hysteresis characterize Ras activation in lymphoid cells.

Cell. 2009 136, 337-351.

Chakraborty et al. and Das et al. (2009) describe how lymphocytes can send either analog or digital Ras-ERK signals depending on the use of the Ras activators RasGRP and SOS.

Ashok Prasad, Julie Zikherman, Jayajit Das, Jeroen Roose, Arthur Weiss, Arup K. Chakraborty.

Origin of the sharp boundary that discriminates positive and negative selection of thymocytes.

PNAS. 2009 Jan 13;106(2):528-33.

Prasad et al. (2009) developed computational models for lymphocyte Ras activation to formulate hypotheses on thymocytes development.

Relevant earlier papers

Roose J, Mollenauer M, Ho M, Kurosaki T, and Weiss A.

Unusual Interplay of Two Types of Ras Activators, RasGRP and SOS, Establishes Robust and Controlled Ras Activation in Lymphocytes.

Mol Cell Biol. 2007 27(7):2732-45

Roose J, Mollenauer M, Gupta V, Stone J, and Weiss A.

A Diacylglycerol-Protein Kinase C-RasGRP1 Pathway Directs Ras Activation Upon Antigen Receptor Stimulation of T cells.

Mol. Cell Biol. 2005 25(11);4426-41.

Roose J, Diehn M, Tomlinson M, Lin J, Alizadeh A, Botstein D, Brown P, Weiss A.

T cell Receptor-Independent Basal Signaling via Erk and Abl Kinases Suppresses RAG gene Expression.

PLOS Biology. 2003 1(2):271-287.

Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldschmeding R, Logtenberg T, Clevers H.

Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1.

Science. 1999 Sep 17;285(5435):1923-6.


Robert L. Kortum, Alexander Rouquette-Jazdanian, Michihiko Miyaji, Robert K. Merrill, Evan Markegard, John M. Pinski, Amelia Wesselink, Nandan N. Nath, Clayton P. Alexander, Wenmei Li, Noemi Kedei, Jeroen P. Roose, Peter M. Blumberg, Lawrence E. Samelson, and Connie L. Sommers

A PLC-gamma1-independent, RasGRP1-ERK dependent pathway drives lymphoproliferative disease in LAT-Y136F mutant mice

Journal of Immunology. 2012, Dec. 3

Catherine Hartzell*, Olga Ksionda*, Ed Lemmens*, Kristen Coakley, Ming Yang, Richard Harvey, Chris Govern, Jeroen Bakker, Tineke Lenstra, Monique Dail, Kristin Ammon, Anne Boeter, Mignon Loh, Stuart Winter, Arup Chakraborty, Kevin Shannon, Matthias Wabl, and Jeroen Roose.

Dysregulated RasGRP1 Responds to Cytokine Receptor-input in T cell leukemogenesis

Science Signaling. March 26, 2013.     




Hartzell et al. (2013). Growth of T cell leukemia cells.

Highlighted 1
Highlighted 2;6/268/eg3

Jesse Jun, Ming Yang, Hang Chen, Arup Chakraborty, and Jeroen Roose.

Activation of ERK but not of P38 MAP kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS

Mol. Cell. Biology, April, 2013     


Jun et al. (2013).

A SOS1-P38 pathway.


Arup K. Chakraborty and Jeroen P. Roose.

Biochemical heterogeneity and developmental varieties in T-cell leukemia

Cell Cycle. May 15, 2013.  



Jesse Jun, Ignacio Rubio, and Jeroen P. Roose.

Regulation of RasGRP and SOS Ras Exchange Factors by Lipid Messengers and Cellular Localization of Ras activation in T cells.

Frontiers in Immunology, September 4, 2013.                                                                                                                                                                             

Olga Ksionda, Andre Limnander, and Jeroen P. Roose.

RasGRP Ras Guanine Nucleotide Exchange Factors in Cancer.

Frontiers in Biology. October, 2013.                                                                                                                                                                                             

Jeffrey S. Iwig, Yvonne Vercoulen, Rahul Das, Tiago Barros, Andre Limnander, Yan Che, Jeffrey G. Pelton, David E. Wemmer, Jeroen P. Roose# and John Kuriyan#

The Structural Basis for Autoinhibition of the Ras-specific exchange factor RasGRP1.

eLIFE. July 30, 2013.                                                                                                                                                                                              

Highlighted 1Lab_Papers_files/Highlight%20SOS%20activation%202007.pdf

Stephen R. Daley*, Kristen M. Coakley*, Daniel Hu*, Katrina L. Randall*, Craig N. Jenne*, Andre Limnander*, Darienne R. Myers, Noelle K. Polakos, Anselm Enders, Carla Roots, Bhavani Balakishnan, Lisa A. Miosge, Geoff Sjollema, Edward M Bertram, Matthew A Field, Yunli Shao, T. Daniel Andrews, Belinda Whittle, S. Whitney Barnes, John R. Walker, Jason G. Cyster, Christopher C. Goodnow #, and Jeroen P. Roose #.

Rasgrp1 mutation increases naïve T-cell CD44 expression and drives mTOR-dependent accumulation of Helios+ CD44hi CD4+ T cells and autoantibodies.

eLIFE. December 12, 2013.                                                                                            


Iwig et al. (2013).

Autoinhibited RasGRP1 structure




Andre Limnander, Julie Zikherman, Tannia Lau, Michael Leitges, Arthur Weiss and Jeroen P. Roose.

PKCd promotes transitional B cell negative selection and limits proximal BCR signaling to enforce tolerance.

Mol. Cell. Biology. April, 2014.                                                                                                                                                                                                       

Daley et al. (2013). Autoimmune pathology in Rasgrp1-Anaef mice.


Andre Limnander and Jeroen P. Roose.

Global Medical Discovery

April, 2014.                                          

Limnander et al. (2014). PKCd in negative selection of B cells and autoimmunity.


Jeroen Roose and Sidonia Fagarasan

Editorial overview: Lymphocyte development and activation: Lymphocytes, integrators of information

Current Opinion in Immunology. April, 2015.                                             


Philippe Depeille, Linda M. Henricks, Robert A. H. van de Ven, Ed Lemmens, Chih-Yang Wang, Mary Matli, Zena Werb, Kevin M. Haigis, David Donner, Robert Warren, and Jeroen Roose.

RasGRP1 Opposes Proliferative EGFR-SOS1 Ras Signals and Restricts Intestinal Epithelial Cell Growth

Nature Cell Biology. May 2015                                      

PMID: 26005835
PMID: 25776004

Beth A. Lubeck, Philip E. Lapinski, Jennifer A. Oliver, Olga Ksionda, Luis F. Parada, Yuan Zhu, Ivan Maillard, Mark Chiang, Jeroen Roose, and Philip D. King.

Codeletion of the Ras GTPase-Activating Proteins (RasGAPs) Neurofibromin 1 and p120 RasGAP in T Cells Results in the Development of T Cell Acute Lymphoblastic Leukemia

Journal of Immunology. May 2015                                      

PMID: 26002977

Roose et al. (2007) describe how lymphocytes can use two different types of Ras activators; RasGRP or SOS.

Depeille et al. (2015). Suppressive RasGRP1 signals in colorectal cancer.

Philippe Depeille, Robert S. Warren, and Jeroen P. Roose

Unexpected insights for anti-EGFR cancer therapy

Oncotarget. August, 2015.                                             


Olga Ksionda, Alexis A. Melton, Juliane Bache, Milou Tenhagen, Jeroen Bakker, Richard Harvey, Stuart S. Winter, Ignacio Rubio and Jeroen P. Roose

RasGRP1 overexpression in T-ALL increases basal nucleotide exchange on Ras rendering the Ras/PI3K/Akt pathway responsive to pro-tumorigenic cytokines

Oncogene. November 2015.                                             

PMID: 26300054

Philippe Depeille and Jeroen P. Roose

Flavors of EGFR-Ras signals impacting intestinal homeostasis

Cell Cycle. August, 2015.                                             

PMID: 26292152

Ksionda et al. (2015). Constitutive GTP-loading of Ras in RasGRP1 leukemia.

Darienne R. Myers and Jeroen P. Roose

Kinase and Phosphatase Effector Pathways in T cells

Encyclopedia of Immunobiology. 11006. May 2016.                                     

Myers & Roose (2016).

Cartoon of Ras activation by the RasGEFs RasGRP and SOS.


Gemma Rooney, Alice Goodwin, Philippe Depeille, Amnon Sharir, Claude Schofield, Erika Yeh, Jeroen Roose, Ophir Klein, Katherine Rauen, Lauren Weiss, and Erik Ullian

Human iPS cell-derived neurons uncover the impact of increased Ras Signaling in Costello Syndrome

Journal of Neuroscience. January 2016                                            

PMID: 26549032


PMID: 26740656

Marsilius Mues and Jeroen P. Roose

Distinct oncogenic Ras signals characterized by profound differences in flux through the RasGDP/RasGTP cycle

Small GTPases. May 2016.                                

Ernesto Diaz-Flores, Hana Goldschmidt, Philippe Depeille, Victor Ng, Kimberly Krisman, Michael Crone, Olusegun Williams, Benjamin Houseman, Kevan Shokat, Deepak Sampath, Gideon Bollag, Jeroen P. Roose, Benjamin S. Braun, and Kevin Shannon.

PLCgamma and PI3 Kinase Link Cytokine Stimulation to ERK Activation in Primary Hematopoietic Cells Expressing Normal and Oncogenic Kras.                                                                            

Science Signaling. December 3, 2013.                                                                                                                                                                                 

PMID: 27159504

Sune M. Christensen*, Hsiung-Lin Tu*, Jesse Jun*, Steven Alvarez, Meredith Triplet, Jeffrey S. Iwig, Kamlesh Yadav, Dafna Bar-Sagi, Jeroen P. Roose#, Jay T. Groves#

One-way membrane trafficking of SOS in receptor-triggered Ras activation

Nature Structural and Molecular Biology. August 2016

PMID: 27501536

Christensen, Tu, and Jun. (2016). SOS regulation during receptor-Ras signals.

Jeroen P. Roose

Lost GRP on Cytotoxicity?

Nature Immunology. November 2016

PMID: 27849207


Xu Chen, Qiuxia Wu, Philippe Depeille, Peirong Chen, Sophie Thornton, Helen Kalirai, Sarah E. Coupland, Jeroen P Roose, Boris C Bastian.

RasGRP3 mediates MAPK pathway activation in GNAQ mutant uveal melanoma

Cancer Cell. May 2017

Darienne R. Myers*, Tannia Lau*, Evan Markegard, Hyung W. Lim, Herbert Kasler, Minghua Zhu, Andrea Barczak, John P. Huizar, Julie Zikherman, David J. Erle, Weiguo Zhang, Eric Verdin, and Jeroen P. Roose.

Tonic LAT-HDAC7 signals sustain Nur77 and Irf4 expression to tune naïve CD4 T cells

Cell Reports. May 2017

Myers & Lau. (2017). A tonic LAT-HDAC7 signal to curb naive T cells

PMID: 27849207
PMID: 28538176

Darienne R. Myers, Julie Zikherman, and Jeroen P. Roose.

Tonic Signals: Why Do Lymphocytes Bother?

Trends in Immunology. August 2017


Yvonne Vercoulen*, Yasushi Kondo*, Jeffrey S. Iwig*, Axel B. Janssen, Katharine A. White, Mojtaba Amini, Diane L. Barber, John Kuriyan, and Jeroen P. Roose.

A Histidine pH Sensor Regulates Activation of the Ras-specific Guanine Nucleotide Exchange Factor RasGRP1.

eLIFE. September 2017

PMID: 28754596
PMID: 28952923

Vercoulen & Kondo & Iwig (2017). A Histidine pH sensor in RasGRP1..