The Experts below are selected from a list of 3099 Experts worldwide ranked by ideXlab platform
Alberto Corsini - One of the best experts on this subject based on the ideXlab platform.
-
Ajoene, a garlic compound, inhibits Protein Prenylation and arterial smooth muscle cell proliferation
British journal of pharmacology, 2003Co-Authors: Nicola Ferri, Michael H Gelb, Rafael Apitz-castro, Rodolfo Paoletti, Kohei Yokoyama, Martin Sadilek, Alberto CorsiniAbstract:1 Ajoene is a garlic compound with anti-platelet properties and, in addition, was shown to inhibit cholesterol biosynthesis by aAecting 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase and late enzymatic steps of the mevalonate (MVA) pathway. 2 MVA constitutes the precursor not only of cholesterol, but also of a number of non-sterol isoprenoids, such as farnesyl and geranylgeranyl groups. Covalent attachment of these MVA-derived isoprenoid groups (Prenylation) is a required function of several Proteins that regulate cell proliferation. We investigated the eAect of ajoene on rat aortic smooth muscle cell proliferation as related to Protein Prenylation. 3 Cell counting, DNA synthesis, and cell cycle analysis showed that ajoene (1‐50 mM) interfered with the progression of the G1 phase of the cell cycle, and inhibited rat SMC proliferation. 4 Similar to the HMG-CoA reductase inhibitor simvastatin, ajoene inhibited cholesterol biosynthesis. However, in contrast to simvastatin, the antiproliferative eAect of ajoene was not prevented by the addition of MVA, farnesol (FOH), and geranylgeraniol (GGOH). Labelling of smooth muscle cell cellular Proteins with [3H]-FOH and [3H]-GGOH was significantly inhibited by ajoene. 5 In vitro assays for Protein farnesyltransferase (PFTase) and Protein geranylgeranyltransferase type I (PGGTase-I) confirmed that ajoene inhibits Protein Prenylation. High performance liquid chromatography (HPLC) and mass spectrometry analyses also demonstrated that ajoene causes a covalent modification of the cysteine SH group of a peptide substrate for Protein PGGTase-I. 6 Altogether, our results provide evidence that ajoene interferes with the Protein Prenylation reaction, an eAect that may contribute to its inhibition of SMC proliferation.
-
effect of s perillic acid on Protein Prenylation and arterial smooth muscle cell proliferation
Biochemical Pharmacology, 2001Co-Authors: Nicola Ferri, Michael H Gelb, Rodolfo Paoletti, Kohei Yokoyama, Lorenzo Arnaboldi, Augusto Orlandi, Rene Gree, A Granata, Ali Hachem, Alberto CorsiniAbstract:Abstract A number of Proteins post-translationally modified by the covalent attachment of mevalonate-derived isoprene groups farnesol (FOH) or geranylgeraniol (GGOH), play a role in cell proliferation. For this reason, Protein farnesyltransferase (PFTase) and Protein geranylgeranyltransferases (PGGTases) I and II have gained attention as novel targets for the development of antiproliferative agents. Monoterpenes [limonene, perillic acid (PA) and its derivatives] have been shown to inhibit cell growth and Protein Prenylation in cancer cells. In the present study, we evaluated the effect of S (−) PA on diploid rat aorta smooth muscle cell (SMC) proliferation as related to Protein Prenylation. S (−) PA (1–3.5 mM) decreased, in a concentration-dependent manner, rat SMC proliferation as evaluated by cell counting and DNA synthesis. Morphological criteria and flow cytometry analysis excluded the induction of apoptosis as a potential antiproliferative mechanism of S (−) PA on SMC and confirmed a block of the cell cycle progression in G 0 /G 1 phase. The antiproliferative effect of S (−) PA could not be prevented by the addition of mevalonate, FOH, and GGOH to the culture medium and was independent of cholesterol biosynthesis. Densitometric analysis of fluorographed gels, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cell lysates, further supported that S (−) PA (1–3.5 mM), under the same experimental conditions, concentration-dependently inhibited FOH (up to 70%) and GGOH (up to 70%) incorporation into cellular Proteins. We provide evidence that S (−) PA affects Protein Prenylation, an effect that may contribute to its inhibition of SMC proliferation.
Michael H Gelb - One of the best experts on this subject based on the ideXlab platform.
-
therapeutic intervention based on Protein Prenylation and associated modifications
Nature Chemical Biology, 2006Co-Authors: Michael H Gelb, Lucas Brunsveld, Christine A Hrycyna, Susan Michaelis, Fuyuhiko Tamanoi, Wesley C Van Voorhis, Herbert WaldmannAbstract:In eukaryotic cells, a specific set of Proteins are modified by C-terminal attachment of 15-carbon farnesyl groups or 20-carbon geranylgeranyl groups that function both as anchors for fixing Proteins to membranes and as molecular handles for facilitating binding of these lipidated Proteins to other Proteins. Additional modification of these prenylated Proteins includes C-terminal proteolysis and methylation, and attachment of a 16-carbon palmitoyl group; these modifications augment membrane anchoring and alter the dynamics of movement of Proteins between different cellular membrane compartments. The enzymes in the Protein Prenylation pathway have been isolated and characterized. Blocking Protein Prenylation is proving to be therapeutically useful for the treatment of certain cancers, infection by protozoan parasites and the rare genetic disease Hutchinson-Gilford progeria syndrome.
-
Ajoene, a garlic compound, inhibits Protein Prenylation and arterial smooth muscle cell proliferation
British journal of pharmacology, 2003Co-Authors: Nicola Ferri, Michael H Gelb, Rafael Apitz-castro, Rodolfo Paoletti, Kohei Yokoyama, Martin Sadilek, Alberto CorsiniAbstract:1 Ajoene is a garlic compound with anti-platelet properties and, in addition, was shown to inhibit cholesterol biosynthesis by aAecting 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase and late enzymatic steps of the mevalonate (MVA) pathway. 2 MVA constitutes the precursor not only of cholesterol, but also of a number of non-sterol isoprenoids, such as farnesyl and geranylgeranyl groups. Covalent attachment of these MVA-derived isoprenoid groups (Prenylation) is a required function of several Proteins that regulate cell proliferation. We investigated the eAect of ajoene on rat aortic smooth muscle cell proliferation as related to Protein Prenylation. 3 Cell counting, DNA synthesis, and cell cycle analysis showed that ajoene (1‐50 mM) interfered with the progression of the G1 phase of the cell cycle, and inhibited rat SMC proliferation. 4 Similar to the HMG-CoA reductase inhibitor simvastatin, ajoene inhibited cholesterol biosynthesis. However, in contrast to simvastatin, the antiproliferative eAect of ajoene was not prevented by the addition of MVA, farnesol (FOH), and geranylgeraniol (GGOH). Labelling of smooth muscle cell cellular Proteins with [3H]-FOH and [3H]-GGOH was significantly inhibited by ajoene. 5 In vitro assays for Protein farnesyltransferase (PFTase) and Protein geranylgeranyltransferase type I (PGGTase-I) confirmed that ajoene inhibits Protein Prenylation. High performance liquid chromatography (HPLC) and mass spectrometry analyses also demonstrated that ajoene causes a covalent modification of the cysteine SH group of a peptide substrate for Protein PGGTase-I. 6 Altogether, our results provide evidence that ajoene interferes with the Protein Prenylation reaction, an eAect that may contribute to its inhibition of SMC proliferation.
-
effect of s perillic acid on Protein Prenylation and arterial smooth muscle cell proliferation
Biochemical Pharmacology, 2001Co-Authors: Nicola Ferri, Michael H Gelb, Rodolfo Paoletti, Kohei Yokoyama, Lorenzo Arnaboldi, Augusto Orlandi, Rene Gree, A Granata, Ali Hachem, Alberto CorsiniAbstract:Abstract A number of Proteins post-translationally modified by the covalent attachment of mevalonate-derived isoprene groups farnesol (FOH) or geranylgeraniol (GGOH), play a role in cell proliferation. For this reason, Protein farnesyltransferase (PFTase) and Protein geranylgeranyltransferases (PGGTases) I and II have gained attention as novel targets for the development of antiproliferative agents. Monoterpenes [limonene, perillic acid (PA) and its derivatives] have been shown to inhibit cell growth and Protein Prenylation in cancer cells. In the present study, we evaluated the effect of S (−) PA on diploid rat aorta smooth muscle cell (SMC) proliferation as related to Protein Prenylation. S (−) PA (1–3.5 mM) decreased, in a concentration-dependent manner, rat SMC proliferation as evaluated by cell counting and DNA synthesis. Morphological criteria and flow cytometry analysis excluded the induction of apoptosis as a potential antiproliferative mechanism of S (−) PA on SMC and confirmed a block of the cell cycle progression in G 0 /G 1 phase. The antiproliferative effect of S (−) PA could not be prevented by the addition of mevalonate, FOH, and GGOH to the culture medium and was independent of cholesterol biosynthesis. Densitometric analysis of fluorographed gels, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cell lysates, further supported that S (−) PA (1–3.5 mM), under the same experimental conditions, concentration-dependently inhibited FOH (up to 70%) and GGOH (up to 70%) incorporation into cellular Proteins. We provide evidence that S (−) PA affects Protein Prenylation, an effect that may contribute to its inhibition of SMC proliferation.
-
Protein Prenylation: from discovery to prospects for cancer treatment.
Current opinion in chemical biology, 1998Co-Authors: Michael H Gelb, Jeffrey D. Scholten, Judith Sebolt-leopoldAbstract:Abstract A specific set of Proteins in eukaryotic cells contain covalently attached carboxy-terminal prenyl groups (15-carbon farnesyl and 20-carbon geranylgeranyl). Many of them are signaling Proteins including Ras, heterotrimeric G Proteins and Rab Proteins. The Proteins prenyltransferases which attach prenyl groups to Proteins have been well characterized, and an X-ray structure is available for Protein farnesyltransferase. Inhibitors of Protein farnesyltransferase are showing sufficient promise in preclinical trials as anti-cancer drugs to warrant widespread interest in the pharmaceutical industry.
-
Protein Prenylation et cetera signal transduction in two dimensions
Science, 1997Co-Authors: Michael H GelbAbstract:Many signaling Proteins, including the proto-oncogene Ras, require the covalent addition of a lipid chain for proper function. This prenylated Protein is then earmarked for further proteolysis and methylation. In his Perspective, Gelb discusses two reports in this issue that illuminate how the lipid is initially attached to the Protein [Park et al. (p. 1800)] and how the later proteolytic modifications are accomplished [Boyartchuk et al. (p. 1796)]
Anjaneyulu Kowluru - One of the best experts on this subject based on the ideXlab platform.
-
Protein Prenylation in islet β cell function in health and diabetes putting the pieces of the puzzle together
Biochemical Pharmacology, 2015Co-Authors: Anjaneyulu Kowluru, Renu A KowluruAbstract:Post-translational Prenylation involves incorporation of 15-(farnesyl) or 20-(geranylgeranyl) carbon derivatives of mevalonic acid into highly conserved C-terminal cysteines of Proteins. The farnesyl transferase (FTase) and the geranylgeranyl transferase (GGTase) mediate incorporation of farnesyl and geranylgeranyl groups, respectively. At least 300 Proteins are prenylated in the human genome; the majority of these are implicated in cellular processes including growth, differentiation, cytoskeletal function and vesicle trafficking. From a functional standpoint, isoPrenylation is requisite for targeting of modified Proteins to relevant cellular compartments for regulation of effector Proteins. Pharmacological and molecular biological studies have provided compelling evidence for key roles of this signaling pathway in physiological insulin secretion in normal rodent and human islets. Recent evidence indicates that inhibition of Prenylation results in mislocalization of unprenylated Proteins, and surprisingly, they remain in active (GTP-bound) conformation. Sustained activation of G Proteins has been reported in mice lacking GGTase, suggesting alternate mechanisms for the activation of non-prenylated G Proteins. These findings further raise an interesting question if mislocalized, non-prenylated and functionally active G Proteins cause cellular pathology since aberrant Protein Prenylation has been implicated in the onset of cardiovascular disease and diabetes. Herein, we overview the existing evidence to implicate Prenylation in islet function and potential defects in this signaling pathways in the diabetic β-cell. We will also identify critical knowledge gaps that need to be addressed for the development of therapeutics to halt defects in these signaling steps in β cells in models of impaired insulin secretion, metabolic stress and diabetes.
-
phagocyte like nadph oxidase generates ros in ins 832 13 cells and rat islets role of Protein Prenylation
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2011Co-Authors: Ismail Syed, Chandrashekara Kyathanahalli, Anjaneyulu KowluruAbstract:Recent evidence suggests that an acute increase in the generation of phagocyte-like NADPH-oxidase (Nox)-mediated reactive oxygen species (ROS) may be necessary for glucose-stimulated insulin secretion. Using rat islets and INS 832/13 cells, we tested the hypothesis that activation of specific G Proteins is necessary for nutrient-mediated intracellular generation of ROS. Stimulation of β-cells with glucose or a mixture of mitochondrial fuels (mono-methylsuccinate plus α-ketoisocaproic acid) markedly elevated intracellular accumulation of ROS, which was attenuated by selective inhibitors of Nox (e.g., apocynin or diphenyleneiodonium chloride) or short interfering RNA-mediated knockdown of p47phox, one of the subunits of Nox. Selective inhibitors of Protein Prenylation (FTI-277 or GGTI-2147) markedly inhibited nutrient-induced ROS generation, suggesting that activation of one (or more) prenylated small G Proteins and/or γ-subunits of trimeric G Proteins is involved in this signaling axis. Depletion of endogenous GTP levels with mycophenolic acid significantly reduced glucose-induced activation of Rac1 and ROS generation in these cells. Other immunosuppressants, like cyclosporine A or rapamycin, which do not deplete endogenous GTP levels, failed to affect glucose-induced ROS generation, suggesting that endogenous GTP is necessary for glucose-induced Nox activation and ROS generation. Treatment of INS 832/13 cells or rat islets with pertussis toxin (Ptx), which ADP ribosylates and inhibits inhibitory class of trimeric G Proteins (i.e., Gi or Go), significantly attenuated glucose-induced ROS generation in these cells, implicating activation of a Ptx-sensitive G Protein in these signaling cascade. Together, our findings suggest a prenylated Ptx-sensitive signaling step couples Rac1 activation in the signaling steps necessary for glucose-mediated generation of ROS in the pancreatic β-cells.
-
Protein Prenylation in glucose induced insulin secretion from the pancreatic islet β cell a perspective
Journal of Cellular and Molecular Medicine, 2007Co-Authors: Anjaneyulu KowluruAbstract:Insulin secretion from the pancreatic β cell is regulated principally by the ambient concentration of glucose. However, the molecular and cellular mechanisms underlying the stimulus – secretion coupling of glucose-stimulated insulin secretion (GSIS) remain only partially understood. Emerging evidence from multiple laboratories suggests key regulatory roles for GTP-binding Proteins in the cascade of events leading to GSIS. This class of signalling Proteins undergoes a series of requisite post-translational modifications (e.g. Prenylation) at their C-terminal cysteines, which appear to be necessary for their targeting to respective membranous sites for optimal interaction with their respective effector Proteins. This communication represents a perspective on potential regulatory roles for Protein Prenylation steps (i.e. Protein farnesylation and Protein geranylgeranylation) in GSIS from the islet β cell.Possible consequences of Protein Prenylation and potential mechanisms underlying glucose-induced regulation of Prenylation, specifically in the context of GSIS, are also discussed.
Nicola Ferri - One of the best experts on this subject based on the ideXlab platform.
-
Ajoene, a garlic compound, inhibits Protein Prenylation and arterial smooth muscle cell proliferation
British journal of pharmacology, 2003Co-Authors: Nicola Ferri, Michael H Gelb, Rafael Apitz-castro, Rodolfo Paoletti, Kohei Yokoyama, Martin Sadilek, Alberto CorsiniAbstract:1 Ajoene is a garlic compound with anti-platelet properties and, in addition, was shown to inhibit cholesterol biosynthesis by aAecting 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase and late enzymatic steps of the mevalonate (MVA) pathway. 2 MVA constitutes the precursor not only of cholesterol, but also of a number of non-sterol isoprenoids, such as farnesyl and geranylgeranyl groups. Covalent attachment of these MVA-derived isoprenoid groups (Prenylation) is a required function of several Proteins that regulate cell proliferation. We investigated the eAect of ajoene on rat aortic smooth muscle cell proliferation as related to Protein Prenylation. 3 Cell counting, DNA synthesis, and cell cycle analysis showed that ajoene (1‐50 mM) interfered with the progression of the G1 phase of the cell cycle, and inhibited rat SMC proliferation. 4 Similar to the HMG-CoA reductase inhibitor simvastatin, ajoene inhibited cholesterol biosynthesis. However, in contrast to simvastatin, the antiproliferative eAect of ajoene was not prevented by the addition of MVA, farnesol (FOH), and geranylgeraniol (GGOH). Labelling of smooth muscle cell cellular Proteins with [3H]-FOH and [3H]-GGOH was significantly inhibited by ajoene. 5 In vitro assays for Protein farnesyltransferase (PFTase) and Protein geranylgeranyltransferase type I (PGGTase-I) confirmed that ajoene inhibits Protein Prenylation. High performance liquid chromatography (HPLC) and mass spectrometry analyses also demonstrated that ajoene causes a covalent modification of the cysteine SH group of a peptide substrate for Protein PGGTase-I. 6 Altogether, our results provide evidence that ajoene interferes with the Protein Prenylation reaction, an eAect that may contribute to its inhibition of SMC proliferation.
-
effect of s perillic acid on Protein Prenylation and arterial smooth muscle cell proliferation
Biochemical Pharmacology, 2001Co-Authors: Nicola Ferri, Michael H Gelb, Rodolfo Paoletti, Kohei Yokoyama, Lorenzo Arnaboldi, Augusto Orlandi, Rene Gree, A Granata, Ali Hachem, Alberto CorsiniAbstract:Abstract A number of Proteins post-translationally modified by the covalent attachment of mevalonate-derived isoprene groups farnesol (FOH) or geranylgeraniol (GGOH), play a role in cell proliferation. For this reason, Protein farnesyltransferase (PFTase) and Protein geranylgeranyltransferases (PGGTases) I and II have gained attention as novel targets for the development of antiproliferative agents. Monoterpenes [limonene, perillic acid (PA) and its derivatives] have been shown to inhibit cell growth and Protein Prenylation in cancer cells. In the present study, we evaluated the effect of S (−) PA on diploid rat aorta smooth muscle cell (SMC) proliferation as related to Protein Prenylation. S (−) PA (1–3.5 mM) decreased, in a concentration-dependent manner, rat SMC proliferation as evaluated by cell counting and DNA synthesis. Morphological criteria and flow cytometry analysis excluded the induction of apoptosis as a potential antiproliferative mechanism of S (−) PA on SMC and confirmed a block of the cell cycle progression in G 0 /G 1 phase. The antiproliferative effect of S (−) PA could not be prevented by the addition of mevalonate, FOH, and GGOH to the culture medium and was independent of cholesterol biosynthesis. Densitometric analysis of fluorographed gels, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cell lysates, further supported that S (−) PA (1–3.5 mM), under the same experimental conditions, concentration-dependently inhibited FOH (up to 70%) and GGOH (up to 70%) incorporation into cellular Proteins. We provide evidence that S (−) PA affects Protein Prenylation, an effect that may contribute to its inhibition of SMC proliferation.
Kohei Yokoyama - One of the best experts on this subject based on the ideXlab platform.
-
Ajoene, a garlic compound, inhibits Protein Prenylation and arterial smooth muscle cell proliferation
British journal of pharmacology, 2003Co-Authors: Nicola Ferri, Michael H Gelb, Rafael Apitz-castro, Rodolfo Paoletti, Kohei Yokoyama, Martin Sadilek, Alberto CorsiniAbstract:1 Ajoene is a garlic compound with anti-platelet properties and, in addition, was shown to inhibit cholesterol biosynthesis by aAecting 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase and late enzymatic steps of the mevalonate (MVA) pathway. 2 MVA constitutes the precursor not only of cholesterol, but also of a number of non-sterol isoprenoids, such as farnesyl and geranylgeranyl groups. Covalent attachment of these MVA-derived isoprenoid groups (Prenylation) is a required function of several Proteins that regulate cell proliferation. We investigated the eAect of ajoene on rat aortic smooth muscle cell proliferation as related to Protein Prenylation. 3 Cell counting, DNA synthesis, and cell cycle analysis showed that ajoene (1‐50 mM) interfered with the progression of the G1 phase of the cell cycle, and inhibited rat SMC proliferation. 4 Similar to the HMG-CoA reductase inhibitor simvastatin, ajoene inhibited cholesterol biosynthesis. However, in contrast to simvastatin, the antiproliferative eAect of ajoene was not prevented by the addition of MVA, farnesol (FOH), and geranylgeraniol (GGOH). Labelling of smooth muscle cell cellular Proteins with [3H]-FOH and [3H]-GGOH was significantly inhibited by ajoene. 5 In vitro assays for Protein farnesyltransferase (PFTase) and Protein geranylgeranyltransferase type I (PGGTase-I) confirmed that ajoene inhibits Protein Prenylation. High performance liquid chromatography (HPLC) and mass spectrometry analyses also demonstrated that ajoene causes a covalent modification of the cysteine SH group of a peptide substrate for Protein PGGTase-I. 6 Altogether, our results provide evidence that ajoene interferes with the Protein Prenylation reaction, an eAect that may contribute to its inhibition of SMC proliferation.
-
effect of s perillic acid on Protein Prenylation and arterial smooth muscle cell proliferation
Biochemical Pharmacology, 2001Co-Authors: Nicola Ferri, Michael H Gelb, Rodolfo Paoletti, Kohei Yokoyama, Lorenzo Arnaboldi, Augusto Orlandi, Rene Gree, A Granata, Ali Hachem, Alberto CorsiniAbstract:Abstract A number of Proteins post-translationally modified by the covalent attachment of mevalonate-derived isoprene groups farnesol (FOH) or geranylgeraniol (GGOH), play a role in cell proliferation. For this reason, Protein farnesyltransferase (PFTase) and Protein geranylgeranyltransferases (PGGTases) I and II have gained attention as novel targets for the development of antiproliferative agents. Monoterpenes [limonene, perillic acid (PA) and its derivatives] have been shown to inhibit cell growth and Protein Prenylation in cancer cells. In the present study, we evaluated the effect of S (−) PA on diploid rat aorta smooth muscle cell (SMC) proliferation as related to Protein Prenylation. S (−) PA (1–3.5 mM) decreased, in a concentration-dependent manner, rat SMC proliferation as evaluated by cell counting and DNA synthesis. Morphological criteria and flow cytometry analysis excluded the induction of apoptosis as a potential antiproliferative mechanism of S (−) PA on SMC and confirmed a block of the cell cycle progression in G 0 /G 1 phase. The antiproliferative effect of S (−) PA could not be prevented by the addition of mevalonate, FOH, and GGOH to the culture medium and was independent of cholesterol biosynthesis. Densitometric analysis of fluorographed gels, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cell lysates, further supported that S (−) PA (1–3.5 mM), under the same experimental conditions, concentration-dependently inhibited FOH (up to 70%) and GGOH (up to 70%) incorporation into cellular Proteins. We provide evidence that S (−) PA affects Protein Prenylation, an effect that may contribute to its inhibition of SMC proliferation.
-
a Protein geranylgeranyltransferase from bovine brain implications for Protein Prenylation specificity
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: Kohei Yokoyama, John A Glomset, Gary W Goodwin, Farideh Ghomashchi, Michael H GelbAbstract:Abstract A Protein geranylgeranyltransferase (PGT) that catalyzes the transfer of a 20-carbon prenyl group from geranylgeranyl pyrophosphate to a cysteine residue in Protein and peptide acceptors was detected in bovine brain cytosol and partially purified. The enzyme was shown to be distinct from a previously characterized Protein farnesyltransferase (PFT). The PGT selectively geranylgeranylated a synthetic peptide corresponding to the C terminus of the gamma 6 subunit of bovine brain G Proteins, which have previously been shown to contain a 20-carbon prenyl modification. Likewise, a peptide corresponding to the C terminus of human lamin B, a known farnesylated Protein, selectively served as a substrate for farnesylation by the PFT. However, with high concentrations of peptide acceptors, both prenyl transferases were able to use either peptide as substrates and the PGT was able to catalyze farnesyl transfer. Among the prenyl acceptors tested, peptides and Proteins with leucine or phenylalanine at their C termini served as geranylgeranyl acceptors, whereas those with C-terminal serine were preferentially farnesylated. These results suggest that the C-terminal amino acid is an important structural determinant in controlling the specificity of Protein Prenylation.
