This laboratory has been investigating the mechanism leukocyte chemotaxis using the chemoattractant receptors as a model for signal transduction by a G-protein coupled receptor. A role for the G-protein G i-2 in the chemotaxis of macrophage and neutrophils has been demonstrated by this and other laboratories. Studies in this laboratory have demonstrated a role for methylation in chemotaxis and other important biological responses. It has been recently recognized that a number of membrane proteins contain the carboxyl terminal amino acid sequence Cys-Aaa-Aaa-Xaa (where Aaa is an aliphatic and Xaa is any amino acid). The Cys-Aaa-Aaa-Xaa sequence is posttranslationally modified by a multistep process which includes carboxylmethylation of the alpha-carboxyl group of the C-terminal cysteine. We have demonstrated carboxylmethylation and processing of the psi-subunit of brain G i/G o. We have also discovered a GTP-dependent carboxylmethylation for some members of the small molecular weight GTP- binding protein family. One of these methylated proteins has been identified as the GTP-binding protein G25K. The G25K protein has been purified from brain homogenates, and GTP stimulates G25K methylation by increasing the affinity of G25K for the methyltransferase. The data suggest an important role for carboxylmethylation in regulating the localization and function of this class of GTP-binding proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH000942-10
Application #
3859854
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1991
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code