Splice Variants of SmgGDS Control Small GTPase Prenylation and Membrane Localization

• DOI: 10.1074/jbc.m110.129916
• Publication Date: 2010-08-14T00:46:25Z
• Authors: Tracy J. Berg; Adam J. Gastonguay; Ellen L. Lorimer; John R. Kuhnmuench; Rongshan Li; Alan P. Fields; Carol L. Williams
• Keywords: GTP-binding protein regulators; Geranylgeranylation; Small GTPase; Ras superfamily

Ras and Rho small GTPases possessing a C-terminal polybasic region (PBR) are vital signaling proteins whose misregulation can lead to cancer. Signaling by these depends on their ability bind guanine nucleotides prenylation with geranylgeranyl or farnesyl isoprenoid moiety subsequent trafficking cellular membranes. There is little previous evidence that signals restrain nonprenylated from entering the pathway, leading general belief PBR-possessing prenylated as soon they synthesized. Here, we present challenges this belief. We demonstrate insertion of dominant negative mutation inhibit GDP/GTP exchange diminishes Rap1A RhoA, enhances Rac1, does not detectably alter K-Ras. Our results indicate entrance passage through pathway regulated two splice variants SmgGDS, protein has been reported promote be up-regulated in several forms show previously characterized 558-residue SmgGDS variant (SmgGDS-558) selectively associates facilitates plasma membrane, whereas less well 607-residue (SmgGDS-607) regulates entry Rap1A, Rac1 into pathway. These nucleotide interactions regulate