Faculty

JOSEPH ADAMS

Associate Professor of Pharmacology

TEL: 858-822-3360

FAX: 858-822-3361

email:joeadams@chem.ucsd.edu

Ph.D., Pennsylvania State University

Key Words: Protein Kinases; Enzyme Catalysis and Regulation

Our laboratory studies the mechanism of protein phosphorylation, a posttranslational modification that drives most communication pathways in the cell. The enzymes that catalyze this transformation, the protein kinases, are significant owing to their roles in cell growth/differentiation and their potential as drug targets. Our interests center on how protein phosphorylation takes place, how protein kinases recognize their protein substrates and how their activity is regulated. We are currently pursuing two areas of biological interest. First, we are studying the role of protein phosphorylation in the control of mRNA splicing. Here we are investigating the role of a family of splicing factors known as SR proteins that modulate splice site selection and spliceosome assembly through phosphorylation by two unique classes of protein kinases, the SRPK and Clk/Sty families. Of particular interest is the role of phosphorylation in controlling the interaction of SR proteins with spliceosomal components. Second, we are investigating protein kinases involved in T cell function. Specifically, we are analyzing the regulatory properties of Csk, a nonreceptor tyrosine kinase that phosphorylates and down regulates all Src family members. We are exploring how Csk recognizes Src enzymes and how phosphorylation and scaffolding proteins alter this biomolecular interaction.

Some Recent Articles

L. Wong, S. Lieser, B. Chie-Leon, O. Miyashita, B. Aubol, J. Shaffer, J. N. Onuchic, P. A. Jennings, V. L. Woods Jr, J. A. Adams JA. (2004) “Dynamic coupling between the SH2 domain and active site of the COOH terminal Src kinase, Csk” J Mol Biol 341, 93-106.

L. Wong, P. A. Jennings, and J. A. Adams (2004) “Communication pathways between the nucleotide pocket and distal regulatory sites in protein kinases.” Acc Chem Res 37, 304-11.

B. E. Aubol, S. Chakrabarti, J. Ngo, J. Shaffer, B. Nolen, X. D. Fu, G. Ghosh, and J. A. Adams (2003) “Processive phosphorylation of alternative splicing factor/splicing factor 2” Proc Natl Acad Sci U S A 100, 12601-12606

B. Nolen, J. Ngo, S. Chakrabarti, D. Vu, J. A. Adams, and G. Ghosh (2003) "Nucleotide-induced conformational changes in the saccharomyces cerevisiae SR protein kinase, Sky1p, revealed by X-ray crystallography." Biochemistry 42, 9575-85.

M. Valiev, R. Kawai, J. A. Adams, and J. H. Weare (2003). "The role of the putative catalytic base in the phosphoryl transfer reaction in a protein kinase: first-principles calculations." J Am Chem Soc 125, 9926-9927.

J. A. Adams (2003) “Activation loop phosphorylation and catalysis in protein kinases: is there functional evidence for the autoinhibitor model?” Biochemistry 42, 601-7.