Abstract

This grant seeks to better understand the structure and function of protein tyrosine phosphatases (PTP), a superfamily of enzymes playing important roles in signal transduction. Our laboratory has identified a PTP-associated adapter protein in Drosophilia melanogaster known as Dock. Dock plays an essential role in axon guidance in the fly. We have isolated five Dock-associated proteins. We plan to clone and characterize these cDNAs and corresponding proteins in order to better understand their interactions with Dock, the PTP, as well as their roles in axonal guidance. Our goals also include the use of a novel strategy to identify substrates for two S. cerevisae phosphatases, ACR2 and YG4E. We anticipate that our strategies may be extended to understand the functions of other yeast phosphatases. Finally, our laboratory has solved the structure for the first phospholipase D supergene family member. The PLD supergene family members play key roles in signal transduction, vesicle traffic, mitosis, and bacterial pathogenesis. We plan to extend our structural and functional studies to other members of the PLD supergene family.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK018849-30
Application #
6634848
Study Section
Biochemistry Study Section (BIO)
Program Officer
Blondel, Olivier
Project Start
1991-10-01
Project End
2005-05-31
Budget Start
2003-07-01
Budget End
2005-05-31
Support Year
30
Fiscal Year
2003
Total Cost
$482,368
Indirect Cost

  Institution

Name
University of California San Diego
Department
Pharmacology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Banerjee, Sourav; Ji, Chenggong; Mayfield, Joshua E et al. (2018) Ancient drug curcumin impedes 26S proteasome activity by direct inhibition of dual-specificity tyrosine-regulated kinase 2. Proc Natl Acad Sci U S A 115:8155-8160
Zhang, Hui; Zhu, Qinyu; Cui, Jixin et al. (2018) Structure and evolution of the Fam20 kinases. Nat Commun 9:1218
Qiu, Yimin; Poppleton, Erik; Mekkat, Arya et al. (2018) Enzymatic Phosphorylation of Ser in a Type I Collagen Peptide. Biophys J 115:2327-2335
Pollak, Adam J; Haghighi, Kobra; Kunduri, Swati et al. (2017) Phosphorylation of serine96 of histidine-rich calcium-binding protein by the Fam20C kinase functions to prevent cardiac arrhythmia. Proc Natl Acad Sci U S A 114:9098-9103
Cui, Jixin; Zhu, Qinyu; Zhang, Hui et al. (2017) Structure of Fam20A reveals a pseudokinase featuring a unique disulfide pattern and inverted ATP-binding. Elife 6:
Wang, Xiaorong; Cimermancic, Peter; Yu, Clinton et al. (2017) Molecular Details Underlying Dynamic Structures and Regulation of the Human 26S Proteasome. Mol Cell Proteomics 16:840-854
Nguyen, Kim B; Sreelatha, Anju; Durrant, Eric S et al. (2016) Phosphorylation of spore coat proteins by a family of atypical protein kinases. Proc Natl Acad Sci U S A 113:E3482-91
Guo, Xing; Wang, Xiaorong; Wang, Zhiping et al. (2016) Site-specific proteasome phosphorylation controls cell proliferation and tumorigenesis. Nat Cell Biol 18:202-12
Tagliabracci, Vincent S; Wiley, Sandra E; Guo, Xiao et al. (2015) A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell 161:1619-32
He, Yantao; Guo, Xing; Yu, Zhi-Hong et al. (2015) A potent and selective inhibitor for the UBLCP1 proteasome phosphatase. Bioorg Med Chem 23:2798-809

Showing the most recent 10 out of 83 publications