Phosphorylation is the most common covalent modification involved in regulation of metabolism in eukaryotes. This grant supports our studies on the structural and functional properties of protein kinases, their mode of regulation, identification of substrates, and the functional consequences of phosphorylation on activity.
The specific aims to be addressed include the following. I. We will continue studies on the mode of regulation of casein kinase (CK) II by examining phosphorylation of the enzyme in vivo in response to hormones and in vitro in response to various effector compounds. The alpha and beta subunits of CK II are expressed in E. coli and will continue to be characterized alone and as the reconstituted holoenzyme and the effects of site-specific mutations on activity will be examined. II. Sequencing of the DNA coding for casein kinase (CK) I will be completed and the sequence compared with those of other protein kinases. We will continue the physical, chemical, and functional characterization of CK I. Phosphorylation and modulation of activity in cultured cells will also be examined. III. We will examine the effects of autophosphorylation of protease activated kinase (PAK) I on activity, determine whether the protein kinase is modified by other protein kinases, examine potential effectors of protein kinase activity and continue characterization of the enzyme. We will also examine the mode of activation of PAK I in cultured cells. IV. We will examine the requirements for complex association of protein substrates with other proteins/peptides to promote phosphorylation of the substrate and alter activity, using calmodulin as a model system. V. The effects of site-specific and multiple phosphorylation of proteins of interest will continue to be examined and the functional role of single and multiple phosphorylation events on enzyme activity, nucleic acid binding, and on protein/protein interactions will be analyzed.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Biochemistry Study Section (BIO)
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University of California Riverside
Schools of Earth Sciences/Natur
United States
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Hsu, Yuan-Hao; Traugh, Jolinda A (2011) Amide hydrogen/deuterium exchange & MALDI-TOF mass spectrometry analysis of Pak2 activation. J Vis Exp :e3602
Hsu, Yuan-Hao; Traugh, Jolinda A (2010) Reciprocally coupled residues crucial for protein kinase Pak2 activity calculated by statistical coupling analysis. PLoS One 5:e9455
Hsu, Yuan-Hao; Johnson, David A; Traugh, Jolinda A (2008) Analysis of conformational changes during activation of protein kinase Pak2 by amide hydrogen/deuterium exchange. J Biol Chem 283:36397-405
Jung, Jin-Hun; Pendergast, Ann Marie; Zipfel, Patricia A et al. (2008) Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK. Biochemistry 47:1094-104
Ling, Jun; Morley, Simon J; Traugh, Jolinda A (2005) Inhibition of cap-dependent translation via phosphorylation of eIF4G by protein kinase Pak2. EMBO J 24:4094-105
Jung, Jin-Hun; Traugh, Jolinda A (2005) Regulation of the interaction of Pak2 with Cdc42 via autophosphorylation of serine 141. J Biol Chem 280:40025-31
Miah, S M Shahjahan; Sada, Kiyonao; Tuazon, Polygena T et al. (2004) Activation of Syk protein tyrosine kinase in response to osmotic stress requires interaction with p21-activated protein kinase Pak2/gamma-PAK. Mol Cell Biol 24:71-83
Orton, Kevin C; Ling, Jun; Waskiewicz, Andrew J et al. (2004) Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. J Biol Chem 279:38649-57
Huang, Zhongdong; Ling, Jun; Traugh, Jolinda A (2003) Localization of p21-activated protein kinase gamma-PAK/Pak2 in the endoplasmic reticulum is required for induction of cytostasis. J Biol Chem 278:13101-9
Tuazon, Polygena T; Lorenson, Mary Y; Walker, Ameae M et al. (2002) p21-activated protein kinase gamma-PAK in pituitary secretory granules phosphorylates prolactin. FEBS Lett 515:84-8

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