; R o o t E n t r y F C o m p O b j b W o r d D o c u m e n t O b j e c t P o o l 4 @ , - . / 0 1 2 3 4 5 F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; Abstract 9513672 Damuni There is considerable evidence that insulin regulates diverse cellular processes, in part, by causing a marked increase in the phosphoylation of numerous cellular proteins on serine and threonine residues. However, despite substantial progress in recent years, the mechanism underlying this effect of insulin remains unclear. The experiments described in the proposal are designed to test the hypothesis that the mechanism by which insulin causes a marked increase in the phsophorylation of cellular proteins on serines and threonines is mediated in part by: a) the phosphorylation and activation of a distinct insulin-stimulated protein serine threonine kinase (cPK) catalyzed by MBPK-1 and MBPK-2, two new members of the mitogen-activated protein kinase (MAPK) family, b) the phosphorylation and inactivation of protein phosphatase 2A, a major cytoplasmic protein serine threonine phosphatase, and c) by the activation of phosphorylation of MBPK-1 and 2 catalyzed by MAPK kinase. The specific questions addressed in this application are: a) are cPK, PP2A, MBPK-1 and MBPK-2 phos phorylated at regulatory sites in intact cells in response to insulin, and b) are MBPK-1 and MBPK-2 distinct members of the MAPK family of enzymes. To address these questions, a combination of biochemical, immunological and molecular approaches will be employed to determine the location of residues modified on cPK, PP2A, MBPK-1 and MBPK-2 in vitro and in vivo. To establish the relationship of MBPK-1 and MBPK-2 to the MAPK family of enzymes, cDNAs of the former will be isolated, sequenced and expressed, and the recombinant proteins will be purified and characterized. The studies in this application will provide important new information on the mechanism of insulin action. *** ; Oh +' 0 ( L p $ H l NORMAL.DOT Abstract Barbara Zain Barb S u m m a r y I n f o r m a t i o n ( + ara Zain @ @ @ @ Microsoft Word 6.0 2 e = e l l l l l l l ^ 1 # @ T 4 ^ l ^ l l l l l l l l Q Abstract 9513672 Damuni There is considerable evidence that insulin regulates diverse cellular processes, in part, by causing a marked increase in the phosphoylation of numerous cellular proteins on serine and threonine residues. However, despite substantial progress in recent years, the mechanism underlying this effect of insulin remains unclear. The experiments described in the proposal are designed to test the hypothesis that the mechanism by which insulin causes a marked increase in the phsophorylation of cellular proteins on serines and threonines is mediated in part by: a) the phosphorylation and activation of a distinct insulin-stimulated protein serine threonine kinase (cPK) catalyzed by MBPK-1 and MBPK-2, two new members of the mitogen-activated protein kinase (MAPK) family, b) the phosphorylation and inactivation of protein phosphatase 2A, a major cytoplasmic protein serine threonine phosphatase, and c) by the activation of phosphorylation of MBPK-1 and 2 catalyzed by MAPK kinase. The specific questions addressed in this application are: a) are cP

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Application #
9513672
Program Officer
Richard Rodewald
Project Start
Project End
Budget Start
1996-02-01
Budget End
2000-01-31
Support Year
Fiscal Year
1995
Total Cost
$339,374
Indirect Cost
Name
Pennsylvania State University
Department
Type
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802