Rab 11a is modified in vivo by isoprenoid geranylgeranyl

Post‐translational adduction of farnesyl or geranylgeranyl moieties to a terminal cysteine residue of proteins is a characteristic feature of ras ‐related GTP‐binding proteins. According to current rules of prenylation the carboxylterminal motif (CXXX or CC/CXC) as well the context of the cysteine residue dictate the extend and specificity of the isoprenoid modification. Rab 11a, a small GTP‐binding protein that is associated with pathways regulating protein traffic, terminates with isoleucine at its C ‐terminus, suggesting that it may only be geranylgeranylated. Recent finding, however, showed that rab 11a can be modified in vitro by different prenyl groups: farnesyl and geranylgeranyl [1]. To determine whether rab 11a is modified in vivo by both isoprenoids we transiently overexpressed rab 11a in COS1 cells, and analyzed the translation products by two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE) in combination with metabolic labeling in the presence of either [ 3 H]farnesyl‐PP or [ 3 H]geranylgeranyl‐PP. Contrary to the in vitro results, our studies showed that rab 11a is post‐translationally modified in vivo only by geranylgeranyl isoprenoid. The data implied that in vivo there must exist other determinant(s) that are necessary for prenyltransferase recognition.