Immunology Graduate Program | University of California, San Francisco

Arthur Weiss, MD, PhD

Signal Transduction Events in T Lymphocytes

Ephraim P. Engleman Distinguished Professor
Department of Medicine, Division of Rheumatology
Department of Microbiology and Immunology
513 Parnassus, Room S-1032C, Box 0795
San Francisco, CA 94143-0795

(415) 476-8983 tel
(415) 502-5081 fax
aweiss@medicine.ucsf.edu

AA: Mary Anne Ford
415-476-1291 tel

Description of Research

The response of lymphocytes to antigen presents a unique opportunity to study how complex molecular interactions between cells can lead to developmental decisions, cell differentiation and proliferation. We are interested in understanding how receptors involved in antigen recognition can initiate signal transduction events that regulate cell responses in the immune system. We know that receptors involved in antigen recognition functionally interact with tyrosine kinases and phosphatases, enzymes that regulate protein phosphorylation, to induce signaling pathways that regulate gene expression. We would like to understand how the molecules in these pathways are regulated and how they control cellular responses in development, in normal immune responses and in autoimmune diseases such as lupus and rheumatoid arthritis.

Brdicka, T., Kadlecek, T.A., Roose, J.P., Pastuszak, A.W., and Weiss, A . Intramolecular regulatory switch in ZAP-70: analogy to with receptor tyrosine kinases. Mol. Cell. Biol. 25:4924-4933, 2005.

Deindl, S., Kadlecek, T.A. , Brdicka, T., Cao, X., Weiss, A., and Kuriyan, J. Structural basis for the inhibition of the tyrosine kinase activity of ZAP-70. Cell , 129:735-746, 2007.

Hermiston, M., Tan, A.L., Gupta, V.A., Majeti, R., and Weiss, A. The juxtamembrane wedge negatively, regulates CD45 function in B cells. Immunity 23:635-647, 2005.

Myers, M.D., Dragone, L.L., and Weiss, A . Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 expression by targeting TCR z for degradation. J. Cell Biol . 170:285-294, 2005.

Myers, M.D., Sosinowski, T., Dragone, L.L., White, C., Band, H., Gu, H., and Weiss, A. Src-like adaptor protein regulates TCR expression on thymocytes by adapting c-Cbl to the TCR complex. Nature Immunol ., 7:57-66, 2006.

Palacios, E., and Weiss, A. Distinct roles for Syk and ZAP-70 during thymic development. J. Exp. Med. , 204:1703-1715, 2007.

Phee, H., Abraham, R., and Weiss, A . Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1. Nature Immunol . 6:608-617, 2005.

Roose, J.P., Mollenauer, M., Ho, M., Kurosaki, T., and Weiss, A. Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes, Mol. Cell. Biol. , 27:2732-2735, 2007.