PT  - JOURNAL ARTICLE
AU  - Y Xu
AU  - B A Gilbert
AU  - R R Rando
AU  - L Chen
AU  - A H Tashjian, Jr
TI  - Inhibition of capacitative Ca2+ entry into cells by farnesylcysteine analogs.
DP  - 1996 Dec 01
TA  - Molecular Pharmacology
PG  - 1495--1501
VI  - 50
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/50/6/1495.short
4100  - http://molpharm.aspetjournals.org/content/50/6/1495.full
SO  - Mol Pharmacol1996 Dec 01; 50
AB  - Capacitative Ca2+ influx, which occurs in response to mobilization of intracellular Ca2+ stores, is a general feature of many cell types. Although the mechanism of capacitative Ca2+ entry is not known, evidence suggests the involvement of small G proteins that are prenylated on a cysteine residue near their carboxyl termini. We have investigated the actions of farnesyl-cysteine analogs on capacitative Ca2+ influx. Using human embryonic kidney 293 cells, we found that S-farnesylthioacetic acid, N-acetyl-S-farnesyl-L-cysteine, N-pivaloyl-S-farnesyl-L-cysteine, and N-acetyl-S-gernylgernyl-L-cysteine blocked the activation of capacitative Ca2+ influx, whereas N-benzoyl-S-farnesyl-S-cysteine had no effect on capacitative Ca2+ entry. Inhibition by S-farnesylthioacetic acid was concentration dependent (5-20 microM) and specific for Ca2+ influx through non-voltage-gated Ca2+ channels. A single protein band of 26-28 kDa was labeled specifically with a photoaffinity analog of farnesylcysteine. GTP binding to the photoaffinity-labeled band was demonstrated. These findings suggest, but do not prove, that a prenylated substrate, possibly a small G protein, is linked functionally to capacitative Ca2+ entry in human embryonic kidney 293 cells.