Faculty

VIVIAN Y. H. HOOK

Professor of Pharmacology
Adjunct Professor of Medicine and Neurosciences

School of Pharmacy and Pharmaceutical Sciences

TEL: 858-822-6682
FAX: 858-822-6681

email:vhook@ucsd.edu

Ph.D., University of California, San Francisco

Key Words: Peptide Neurotransmitters, Proteases, Protease Inhibitors, Protein Biochemistry, Neurodegenerative Disease, Proteomics

Our laboratory investigates protease mechanisms required for production of peptide neurotransmitters and hormones that mediate cell-cell communication. Investigation of selective protease pathways provides knowledge of regulatory components involved in the biosynthesis of beneficial peptides required for normal neuroendocrine functions. This research on neuroproteases extends to those involved in neurodegenerative diseases, including Alzheimer's disease. Our protease research strives to understand their regulatory roles in producing active peptides in health and disease.

Selected Publications

Yasothornsrikul, S., Aaron, W., Toneff, T., and Hook, V.Y.H. (1999) Evidence for the proenkephalin processing enzyme 'prohormone thiol protease' (PTP) as a multicatalytic cysteine protease complex; activation by glutathione localized to secretory vesicles. Biochemistry 38, 7421-7430.

Hwang, S.R., Steineckert, B., Toneff, T., Bundey, R., Logvinova, A.V., Goldsmith, P., and Hook, V.Y.H. (2002) The novel serpin endopin 2 demonstrates cross-class inhibition of papain and elastase: localization of endopin 2 to regulated secretory vesicles of neuroendocrine chromaffin cells. Biochemistry 41, 10397-10405

Hook, V.Y.H., and Reisine, T.D. (2003) Cysteine proteases are the major ß-secretase activity in the regulated secretory pathway which provides most of the ß-amyloid (Aß) of Alzheimer's disease: role of BACE 1 in the constitutive secretory pathway. J. Neurosci. Research 74, 393-405.

Miller, R., Toneff, T., Vishynuvardhan, D., Beinfeld, M., and Hook, V.Y.H. (2003) Selective roles for the PC2 processing enzyme in the regulation of peptide neurotransmitter levels in brain and peripheral neuroendocrine tissues of PC2 deficient mice. Neuropeptides 37, 140-148.

Yasothornsrikul, S., Greenbaum, D., Medzihradszky, K.F., Toneff, T., Bundey, R., Miller, R., Schilling, B., Petermann, I., Dehnert, J., Logvinova, A., Goldsmith, P., Gibson, B., Reinheckel, T., Peters, C., Bogyo, M., and Hook, V. (2003) Cathepsin L in secretory vesicles functions as a processing enzyme for production of the enkephalin peptide neurotransmitter. Proc. Natl. Acad. Sci. USA 100, 9590-9595.

Hook, V., Yasothornsrikul, S., Greenbaum, D., Medzihradszky, K.F., Troutner, K., Toneff, T., Bundey, R., Reinheckel, T., Peters, C., and Bogyo, M. (2004) Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway for the biosynthesis of peptide neurotransmitters and hormones. Biol. Chem. 385, 473-480.