Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase.

Inglese, James; Glickman, J. Fraser; Lorenz, Wulfing; Caron, Marc G.; Lefkowitz, Robert J.

doi:10.1016/s0021-9258(18)45960-1

“…Another mechanism that allows a subset of signaling proteins to become enriched in the outer segment is based on their lipid modifications. Examples of phototransduction proteins containing such lipids include PDE, whose a and b subunits are modified by farnesyl and geranylgeranyl groups, respectively ; Ga t , which is acylated by a heterogeneous group of fatty acids (Neubert et al, 1992;Kokame et al, 1992); Gg t , which is farnesylated (Fukada et al, 1990); and the opsin kinase, which is farnesylated in rods (GRK1; Inglese et al, 1992; and geranylgeranylated in cones (GRK7; Hisatomi et al, 1998). While lipid modifications serve to concentrate signaling proteins on the disc membrane, they do not by themselves specify a protein for delivery to the outer segment.…”

Section: Outer Segment Localization Through Lipid Modificationsmentioning

confidence: 99%

Beyond Counting Photons: Trials and Trends in Vertebrate Visual Transduction

Burns

¹

,

Arshavsky

²

2005

Neuron

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For over 30 years, photoreceptors have been an outstanding model system for elucidating basic principles in sensory transduction and G protein signaling. Recently, photoreceptors have become an equally attractive model for studying many facets of neuronal cell biology. The primary goal of this review is to illustrate this rapidly growing trend. We will highlight the areas of active research in photoreceptor biology that reveal how different specialized compartments of the cell cooperate in fulfilling its overall function: converting photon absorption into changes in neurotransmitter release. The same trend brings us closer to understanding how defects in photoreceptor signaling can lead to cell death and retinal degeneration.

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“…These GRKs are posttranslationally modified to ensure their proper subcellular localization within the photoreceptor cells. GRK1 differs slightly from GRK7 in this regard in that GRK1 is posttranslationally modified via farnesylation and blocking this farnesylation markedly limits its ability to phosphorylate activated rhodopsin (Inglese et al 1992). In addition to the prenylation site, GRK1 has been shown to autophosphorylate and that this can affect the affinity of GRK1 toward its substrates including activated rhodopsin (Buczylko et al 1991).…”

Section: Grk1 Subfamilymentioning

confidence: 99%

“…In contrast, based on the sequence of GRK7, it is predicated to have a geranylgeranyl modification site on its C-terminus rather than its N-terminus like GRK1. It is possible that these posttranslational modifications serve as hydrophobic anchors that secure GRK1 and GRK7 to the membranes of these photoreceptor cells (Inglese et al 1992). Although much has been accomplished with the X-ray structure of GRK1, there is still work to be done deciphering the differences and similarities between GRK1 and GRK7 on a molecular and functional scale.…”

Section: Grk1 Subfamilymentioning

confidence: 99%

Grb10

Kabir¹,

Rönnstrand²,

Kazi³

2018

Encyclopedia of Signaling Molecules

0

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G alpha o 1893G regulators of the Gao protein may provide a cellspecific mechanism for Gao-regulated signaling pathways. PTX catalyzes the ADP-ribosylation of the a subunits of the Go, Gi, and Gt proteins at the C-terminal cysteine residue (À4 position). This prevents the G protein from interacting with GPCRs on the cell membrane, thus interfering with intracellular signaling. 1896 G alpha o G alpha o 1897 G cyclase, guanylate cyclase, Rap1 GTPaseactivating protein (Rap1GAP), axin, and pins. Compartmentalization of these signaling molecules in membrane rafts may ensure specificity and fidelity in Gao signaling. Go is the most abundant G protein in the central nervous system, where it comprises about 1% of membrane proteins in the mammalian brain. Go regulates neuronal development, memory, visual reception, olfactory reception, and taste reception. It is also localized in heart tissue and implicated in heart contractility. Its expression is regulated during the development of the brain and heart. Somatic mutations in the GNAO1 gene induce human cancers by rendering Gao constitutively activated. Heterozygous mutations in the GNAO1 gene cause epileptic encephalopathy by destabilizing Gao. Gao-deficient mice have several neurological deficits, including tremors, seizures, hyperalgesia, motor control impairment, and olfactory impairment. Muscarinic regulation of heart rate and heart rate variability is also impaired in Gao-deficient mice. Drosophila melanogaster mutants with loss of function of Gao show impaired morphogenesis of the heart and epithelial polarity of cardiac cells and abnormal sleep. Gao-deficient C. elegans has phenotypes including neuronal migration defects, hyperactive locomotion, and egg laying.

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“…Isoprenylation occurs at the CaaX box motif (C, cysteine; a, any aliphatic residue; X, the residue that determines the type of isoprenoid group attached) (McTaggart 2006). The very C-terminus of GRK1 contains a CaaX box motif (C 558 VLS) to promote isoprenylation (Inglese et al 1992). The last three residues are proteolytic removed and a farnesyl group (15 carbon unit) is covalently linked to cysteine through a thioester bond.…”

Section: Distribution and Physiological Functions Of Gpr120mentioning

confidence: 99%

Gaba

2018

Encyclopedia of Signaling Molecules

0

View full text Add to dashboard Cite

G alpha o 1893G regulators of the Gao protein may provide a cellspecific mechanism for Gao-regulated signaling pathways. PTX catalyzes the ADP-ribosylation of the a subunits of the Go, Gi, and Gt proteins at the C-terminal cysteine residue (À4 position). This prevents the G protein from interacting with GPCRs on the cell membrane, thus interfering with intracellular signaling. 1896 G alpha o G alpha o 1897 G cyclase, guanylate cyclase, Rap1 GTPaseactivating protein (Rap1GAP), axin, and pins. Compartmentalization of these signaling molecules in membrane rafts may ensure specificity and fidelity in Gao signaling. Go is the most abundant G protein in the central nervous system, where it comprises about 1% of membrane proteins in the mammalian brain. Go regulates neuronal development, memory, visual reception, olfactory reception, and taste reception. It is also localized in heart tissue and implicated in heart contractility. Its expression is regulated during the development of the brain and heart. Somatic mutations in the GNAO1 gene induce human cancers by rendering Gao constitutively activated. Heterozygous mutations in the GNAO1 gene cause epileptic encephalopathy by destabilizing Gao. Gao-deficient mice have several neurological deficits, including tremors, seizures, hyperalgesia, motor control impairment, and olfactory impairment. Muscarinic regulation of heart rate and heart rate variability is also impaired in Gao-deficient mice. Drosophila melanogaster mutants with loss of function of Gao show impaired morphogenesis of the heart and epithelial polarity of cardiac cells and abnormal sleep. Gao-deficient C. elegans has phenotypes including neuronal migration defects, hyperactive locomotion, and egg laying.

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Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase.

Cited by 173 publications

References 31 publications

Beyond Counting Photons: Trials and Trends in Vertebrate Visual Transduction

Beyond Counting Photons: Trials and Trends in Vertebrate Visual Transduction

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