The overall goal of this Program Project Group is to understand the mechanisms underlying renal fluid, electrolyte and macromolecule transport. Kinase and phosphatases are essential regulators of this process and thus, by extension, their target phosphorylation sites are important for mechanistic insight. This core will add value to the project group by bringing new capabilities and expertise in the identification and characterization of phosphorylation sites in proteins and proteomes. Dr. Jesse Rinehart will assume the role as the Phosphoproteomics Core Director and will bring expertise in phosphorylation mapping, quantitative proteomics, and phosphoprotein synthesis to the Program Project Group. Dr. Rinehart recently developed a new technology which enables site-specific incorporation of phosphoserine into proteins. This technology enables the synthesis of physiologically relevant phosphoproteins in an E. coli strain with an expanded genetic code. This unique technology and a recently published next- generation phosphoserine technology will be uniquely available to this Program Project Group. The combinations of established phosphoproteomics technologies and novel phosphoprotein synthesis technologies will enable a unique approach to validation and further exploration of the mechanisms of protein phosphorylation. The core will be an excellent learning environment and bring trainees from the Program Project Groups in close contact with proteomics experts in the Rinehart lab. This training environment will provide access to state-of-the-art technology to the individual members of the Project Group. Dr. Rinehart's research interests are closely aligned with the aims of this project group and, in addition to the technology, the unique lab environment is value added to the Program Project Group.

Public Health Relevance

The purpose of this Phosphoproteomics Core is to provide a fundamental connection to the understanding of protein phosphorylation and the mechanisms that coordinate electrolyte homeostasis. This knowledge is essential and will benefit human health.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
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Special Emphasis Panel (ZDK1-GRB-9 (M6))
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Yale University
New Haven
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Han, Jaeyong; Lee, Seung Hun; Giebisch, Gerhard et al. (2016) Potassium Channelopathies and Gastrointestinal Ulceration. Gut Liver 10:881-889
Stoops, Emily H; Hull, Michael; Caplan, Michael J (2016) Newly synthesized and recycling pools of the apical protein gp135 do not occupy the same compartments. Traffic 17:1272-1285
Ishizawa, Kenichi; Xu, Ning; Loffing, Johannes et al. (2016) Potassium depletion stimulates Na-Cl cotransporter via phosphorylation and inactivation of the ubiquitin ligase Kelch-like 3. Biochem Biophys Res Commun 480:745-751
Ferdaus, Mohammed Z; Barber, Karl W; López-Cayuqueo, Karen I et al. (2016) SPAK and OSR1 play essential roles in potassium homeostasis through actions on the distal convoluted tubule. J Physiol 594:4945-66
Scholl, Ute I; Stölting, Gabriel; Nelson-Williams, Carol et al. (2015) Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. Elife 4:e06315
Chen, Tiane; Kocinsky, Hetal S; Cha, Boyoung et al. (2015) Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: identification of a multifunctional phosphorylation site. J Biol Chem 290:1952-65
Oza, Javin P; Aerni, Hans R; Pirman, Natasha L et al. (2015) Robust production of recombinant phosphoproteins using cell-free protein synthesis. Nat Commun 6:8168
Lin, Dao-Hong; Yue, Peng; Yarborough 3rd, Orlando et al. (2015) Src-family protein tyrosine kinase phosphorylates WNK4 and modulates its inhibitory effect on KCNJ1 (ROMK). Proc Natl Acad Sci U S A 112:4495-500
Pirman, Natasha L; Barber, Karl W; Aerni, Hans R et al. (2015) A flexible codon in genomically recoded Escherichia coli permits programmable protein phosphorylation. Nat Commun 6:8130
Farr, Glen A; Hull, Michael; Stoops, Emily H et al. (2015) Dual pulse-chase microscopy reveals early divergence in the biosynthetic trafficking of the Na,K-ATPase and E-cadherin. Mol Biol Cell 26:4401-11

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