Abstract

Lipids covalently modify many proteins involved in membrane- bound signaling systems.In contrast to myristoylation and prenylation, modification by palmitoylation is reversible. The hypothesis to be tested in this proposal is that palmitoylation is a mechanism for regulating protein activity. To test this hypothesis, the heterotrimeric G proteins will be used as a model system to study how palmitate attachment regulates protein activity. The following specific aims are proposed: 1) purification of palmitoylated and non- palmitoylated G protein alpha subunits; 2) comparison of palmitoylated and non-palmitoylated proteins in various assays of G protein activity; 3) purification and characterization of the palmitoyltransferase that catalyzes the covalent attachment of palmitate to these proteins; and 4) isolation of a cDNA clone encoding the palmitoyltransferase.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM051466-01
Application #
2190015
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1994-08-01
Project End
1998-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Physiology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Linder, Maurine E; Jennings, Benjamin C (2013) Mechanism and function of DHHC S-acyltransferases. Biochem Soc Trans 41:29-34
Nishimura, Akiyuki; Linder, Maurine E (2013) Identification of a novel prenyl and palmitoyl modification at the CaaX motif of Cdc42 that regulates RhoGDI binding. Mol Cell Biol 33:1417-29
Hilgemann, Donald W; Fine, Michael; Linder, Maurine E et al. (2013) Massive endocytosis triggered by surface membrane palmitoylation under mitochondrial control in BHK fibroblasts. Elife 2:e01293
Lai, Jianbin; Linder, Maurine E (2013) Oligomerization of DHHC protein S-acyltransferases. J Biol Chem 288:22862-70
Jennings, Benjamin C; Linder, Maurine E (2012) DHHC protein S-acyltransferases use similar ping-pong kinetic mechanisms but display different acyl-CoA specificities. J Biol Chem 287:7236-45
Aittaleb, Mohamed; Nishimura, Akiyuki; Linder, Maurine E et al. (2011) Plasma membrane association of p63 Rho guanine nucleotide exchange factor (p63RhoGEF) is mediated by palmitoylation and is required for basal activity in cells. J Biol Chem 286:34448-56
Jia, Lixia; Linder, Maurine E; Blumer, Kendall J (2011) Gi/o signaling and the palmitoyltransferase DHHC2 regulate palmitate cycling and shuttling of RGS7 family-binding protein. J Biol Chem 286:13695-703
Ahearn, Ian M; Tsai, Frederick D; Court, Helen et al. (2011) FKBP12 binds to acylated H-ras and promotes depalmitoylation. Mol Cell 41:173-85
Hang, Howard C; Linder, Maurine E (2011) Exploring protein lipidation with chemical biology. Chem Rev 111:6341-58
Jernigan, Kristin K; Cselenyi, Christopher S; Thorne, Curtis A et al. (2010) Gbetagamma activates GSK3 to promote LRP6-mediated beta-catenin transcriptional activity. Sci Signal 3:ra37

Showing the most recent 10 out of 38 publications