Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 31 October 2006
Vol. 2006, Issue 359, p. re14
[DOI: 10.1126/stke.3592006re14]

REVIEWS

Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules

Marilyn D. Resh*

Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 143, New York, NY 10021, USA.

Abstract: Palmitate, a 16-carbon saturated fatty acid, is attached to more than 100 proteins. Modification of proteins by palmitate has pleiotropic effects on protein function. Palmitoylation can influence membrane binding and membrane targeting of the modified proteins. In particular, many palmitoylated proteins concentrate in lipid rafts, and enrichment in rafts is required for efficient signal transduction. This Review focuses on the multiple effects of palmitoylation on the localization and function of ligands, receptors, and intracellular signaling proteins. Palmitoylation regulates the trafficking and function of transmembrane proteins such as ion channels, neurotransmitter receptors, heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors, and integrins. In addition, immune receptor signaling relies on protein palmitoylation at many levels, including palmitoylated co-receptors, Src family kinases, and adaptor or scaffolding proteins. The localization and signaling capacities of Ras and G proteins are modulated by dynamic protein palmitoylation. Cycles of palmitoylation and depalmitoylation allow H-Ras and G protein {alpha} subunits to reversibly bind to and signal from different intracellular cell membranes. Moreover, secreted ligands such as Hedgehog, Wingless, and Spitz use palmitoylation to regulate the extent of long- or short-range signaling. Finally, palmitoylation can alter signaling protein function by direct effects on enzymatic activity and substrate specificity. The identification of the palmitoyl acyltransferases has provided new insights into the biochemistry of this posttranslational process and permitted new substrates to be identified.

*Corresponding author. E-mail, m-resh{at}ski.mskcc.org

Citation: M. D. Resh, Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules. Sci. STKE 2006, re14 (2006).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Distinct Palmitoylation Events at the Amino-terminal Conserved Cysteines of Env7 Direct Its Stability, Localization, and Vacuolar Fusion Regulation in S. cerevisiae.
S. P. Manandhar, E. N. Calle, and E. Gharakhanian (2014)
J. Biol. Chem. 289, 11431-11442
   Abstract »    Full Text »    PDF »
What Can Proteomics Tell Us About Platelets?.
J. M. Burkhart, S. Gambaryan, S. P. Watson, K. Jurk, U. Walter, A. Sickmann, J. W. M. Heemskerk, and R. P. Zahedi (2014)
Circ. Res. 114, 1204-1219
   Abstract »    Full Text »    PDF »
Insulin-Regulated Protein Palmitoylation Impacts Endothelial Cell Function.
X. Wei, H. Song, and C. F. Semenkovich (2014)
Arterioscler Thromb Vasc Biol 34, 346-354
   Abstract »    Full Text »    PDF »
Characterization of a Serine Hydrolase Targeted by Acyl-protein Thioesterase Inhibitors in Toxoplasma gondii.
L. E. Kemp, M. Rusch, A. Adibekian, H. E. Bullen, A. Graindorge, C. Freymond, M. Rottmann, C. Braun-Breton, S. Baumeister, A. T. Porfetye, et al. (2013)
J. Biol. Chem. 288, 27002-27018
   Abstract »    Full Text »    PDF »
Local palmitoylation cycles define activity-regulated postsynaptic subdomains.
Y. Fukata, A. Dimitrov, G. Boncompain, O. Vielemeyer, F. Perez, and M. Fukata (2013)
J. Cell Biol. 202, 145-161
   Abstract »    Full Text »    PDF »
Palmitoylation of Amyloid Precursor Protein Regulates Amyloidogenic Processing in Lipid Rafts.
R. Bhattacharyya, C. Barren, and D. M. Kovacs (2013)
J. Neurosci. 33, 11169-11183
   Abstract »    Full Text »    PDF »
Heterodimerization With the Prostacyclin Receptor Triggers Thromboxane Receptor Relocation to Lipid Rafts.
S. Ibrahim, A. McCartney, N. Markosyan, and E. M. Smyth (2013)
Arterioscler Thromb Vasc Biol 33, 60-66
   Abstract »    Full Text »    PDF »
A Small Novel A-Kinase Anchoring Protein (AKAP) That Localizes Specifically Protein Kinase A-Regulatory Subunit I (PKA-RI) to the Plasma Membrane.
P. P. Burgers, Y. Ma, L. Margarucci, M. Mackey, M. A. G. van der Heyden, M. Ellisman, A. Scholten, S. S. Taylor, and A. J. R. Heck (2012)
J. Biol. Chem. 287, 43789-43797
   Abstract »    Full Text »    PDF »
The diacylglycerol lipases: structure, regulation and roles in and beyond endocannabinoid signalling.
M. Reisenberg, P. K. Singh, G. Williams, and P. Doherty (2012)
Phil Trans R Soc B 367, 3264-3275
   Abstract »    Full Text »    PDF »
Linker for Activation of T-cell Family Member2 (LAT2) a Lipid Raft Adaptor Protein for AKT Signaling, Is an Early Mediator of Alkylphospholipid Anti-leukemic Activity.
C. H. Thome, G. A. dos Santos, G. A. Ferreira, P. S. Scheucher, C. Izumi, A. M. Leopoldino, A. M. Simao, P. Ciancaglini, K. T. de Oliveira, A. Chin, et al. (2012)
Mol. Cell. Proteomics 11, 1898-1912
   Abstract »    Full Text »    PDF »
Opportunities and Challenges for Nutritional Proteomics in Cancer Prevention.
D. F. Romagnolo and J. A. Milner (2012)
J. Nutr. 142, 1360S-1369S
   Abstract »    Full Text »    PDF »
LST1/A Is a Myeloid Leukocyte-specific Transmembrane Adaptor Protein Recruiting Protein Tyrosine Phosphatases SHP-1 and SHP-2 to the Plasma Membrane.
P. Draber, O. Stepanek, M. Hrdinka, A. Drobek, L. Chmatal, L. Mala, T. Ormsby, P. Angelisova, V. Horejsi, and T. Brdicka (2012)
J. Biol. Chem. 287, 22812-22821
   Abstract »    Full Text »    PDF »
A role for aberrant protein palmitoylation in FFA-induced ER stress and {beta}-cell death.
A. C. Baldwin, C. D. Green, L. K. Olson, M. A. Moxley, and J. A. Corbett (2012)
Am J Physiol Endocrinol Metab 302, E1390-E1398
   Abstract »    Full Text »    PDF »
Endothelial Cell Palmitoylproteomic Identifies Novel Lipid-Modified Targets and Potential Substrates for Protein Acyl Transferases.
E. P. Marin, B. Derakhshan, T. T. Lam, A. Davalos, and W. C. Sessa (2012)
Circ. Res. 110, 1336-1344
   Abstract »    Full Text »    PDF »
An Electrostatic Switch Controls Palmitoylation of the Large Conductance Voltage- and Calcium-activated Potassium (BK) Channel.
O. Jeffries, L. Tian, H. McClafferty, and M. J. Shipston (2012)
J. Biol. Chem. 287, 1468-1477
   Abstract »    Full Text »    PDF »
DHHC5 Protein Palmitoylates Flotillin-2 and Is Rapidly Degraded on Induction of Neuronal Differentiation in Cultured Cells.
Y. Li, B. R. Martin, B. F. Cravatt, and S. L. Hofmann (2012)
J. Biol. Chem. 287, 523-530
   Abstract »    Full Text »    PDF »
Palmitoylation influences the function and pharmacology of sodium channels.
F. Bosmans, M. Milescu, and K. J. Swartz (2011)
PNAS 108, 20213-20218
   Abstract »    Full Text »    PDF »
SCIMP, a Transmembrane Adaptor Protein Involved in Major Histocompatibility Complex Class II Signaling.
P. Draber, I. Vonkova, O. Stepanek, M. Hrdinka, M. Kucova, T. Skopcova, P. Otahal, P. Angelisova, V. Horejsi, M. Yeung, et al. (2011)
Mol. Cell. Biol. 31, 4550-4562
   Abstract »    Full Text »    PDF »
Membrane Organization and Lipid Rafts.
K. Simons and J. L. Sampaio (2011)
Cold Spring Harb Perspect Biol 3, a004697
   Abstract »    Full Text »    PDF »
Proteomic Profiling of S-acylated Macrophage Proteins Identifies a Role for Palmitoylation in Mitochondrial Targeting of Phospholipid Scramblase 3.
B. A. Merrick, S. Dhungana, J. G. Williams, J. J. Aloor, S. Peddada, K. B. Tomer, and M. B. Fessler (2011)
Mol. Cell. Proteomics 10, M110.006007
   Abstract »    Full Text »    PDF »
Unconventional myristoylation of large-conductance Ca2+-activated K+ channel (Slo1) via serine/threonine residues regulates channel surface expression.
A. Alioua, M. Li, Y. Wu, E. Stefani, and L. Toro (2011)
PNAS 108, 10744-10749
   Abstract »    Full Text »    PDF »
Subcellular Golgi localization of stathmin family proteins is promoted by a specific set of DHHC palmitoyl transferases.
A. D. Levy, V. Devignot, Y. Fukata, M. Fukata, A. Sobel, and S. Chauvin (2011)
Mol. Biol. Cell 22, 1930-1942
   Abstract »    Full Text »    PDF »
Differential Regulation of Two Palmitoylation Sites in the Cytoplasmic Tail of the {beta}1-Adrenergic Receptor.
D. M. Zuckerman, S. W. Hicks, G. Charron, H. C. Hang, and C. E. Machamer (2011)
J. Biol. Chem. 286, 19014-19023
   Abstract »    Full Text »    PDF »
FERM Domain Phosphoinositide Binding Targets Merlin to the Membrane and Is Essential for Its Growth-Suppressive Function.
T. Mani, R. F. Hennigan, L. A. Foster, D. G. Conrady, A. B. Herr, and W. Ip (2011)
Mol. Cell. Biol. 31, 1983-1996
   Abstract »    Full Text »    PDF »
Differential transformation capacity of Src family kinases during the initiation of prostate cancer.
H. Cai, D. A. Smith, S. Memarzadeh, C. A. Lowell, J. A. Cooper, and O. N. Witte (2011)
PNAS 108, 6579-6584
   Abstract »    Full Text »    PDF »
Ion Channel Regulation by Protein Palmitoylation.
M. J. Shipston (2011)
J. Biol. Chem. 286, 8709-8716
   Abstract »    Full Text »    PDF »
LRP6 Mediates cAMP Generation by G Protein-Coupled Receptors Through Regulating the Membrane Targeting of G{alpha}s.
M. Wan, J. Li, K. Herbst, J. Zhang, B. Yu, X. Wu, T. Qiu, W. Lei, C. Lindvall, B. O. Williams, et al. (2011)
Science Signaling 4, ra15
   Abstract »    Full Text »    PDF »
Palmitoylation regulates raft affinity for the majority of integral raft proteins.
I. Levental, D. Lingwood, M. Grzybek, U. Coskun, and K. Simons (2010)
PNAS 107, 22050-22054
   Abstract »    Full Text »    PDF »
Isoform-specific Targeting and Interaction Domains in Human Nicotinamide Mononucleotide Adenylyltransferases.
C. Lau, C. Dolle, T. I. Gossmann, L. Agledal, M. Niere, and M. Ziegler (2010)
J. Biol. Chem. 285, 18868-18876
   Abstract »    Full Text »    PDF »
Rapid and selective detection of fatty acylated proteins using {omega}-alkynyl-fatty acids and click chemistry.
M. C. Yap, M. A. Kostiuk, D. D. O. Martin, M. A. Perinpanayagam, P. G. Hak, A. Siddam, J. R. Majjigapu, G. Rajaiah, B. O. Keller, J. A. Prescher, et al. (2010)
J. Lipid Res. 51, 1566-1580
   Abstract »    Full Text »    PDF »
The Lack of an Inherent Membrane Targeting Signal Is Responsible for the Failure of the Matrix (M1) Protein of Influenza A Virus To Bud into Virus-Like Particles.
D. Wang, A. Harmon, J. Jin, D. H. Francis, J. Christopher-Hennings, E. Nelson, R. C. Montelaro, and F. Li (2010)
J. Virol. 84, 4673-4681
   Abstract »    Full Text »    PDF »
Proteome Scale Characterization of Human S-Acylated Proteins in Lipid Raft-enriched and Non-raft Membranes.
W. Yang, D. Di Vizio, M. Kirchner, H. Steen, and M. R. Freeman (2010)
Mol. Cell. Proteomics 9, 54-70
   Abstract »    Full Text »    PDF »
GRIN1 Regulates {micro}-Opioid Receptor Activities by Tethering the Receptor and G Protein in the Lipid Raft.
X. Ge, Y. Qiu, H. H. Loh, and P.-Y. Law (2009)
J. Biol. Chem. 284, 36521-36534
   Abstract »    Full Text »    PDF »
The Ca2+ channel {beta} subunit determines whether stimulation of Gq-coupled receptors enhances or inhibits N current.
J. F. Heneghan, T. Mitra-Ganguli, L. F. Stanish, L. Liu, R. Zhao, and A. R. Rittenhouse (2009)
J. Gen. Physiol. 134, 369-384
   Abstract »    Full Text »    PDF »
Orientation of palmitoylated CaV{beta}2a relative to CaV2.2 is critical for slow pathway modulation of N-type Ca2+ current by tachykinin receptor activation.
T. Mitra-Ganguli, I. Vitko, E. Perez-Reyes, and A. R. Rittenhouse (2009)
J. Gen. Physiol. 134, 385-396
   Abstract »    Full Text »    PDF »
Neuronal palmitoyl acyl transferases exhibit distinct substrate specificity.
K. Huang, S. Sanders, R. Singaraja, P. Orban, T. Cijsouw, P. Arstikaitis, A. Yanai, M. R. Hayden, and A. El-Husseini (2009)
FASEB J 23, 2605-2615
   Abstract »    Full Text »    PDF »
Palmitoylation-Dependent Plasma Membrane Transport but Lipid Raft-Independent Signaling by Linker for Activation of T Cells.
M. Hundt, Y. Harada, L. De Giorgio, N. Tanimura, W. Zhang, and A. Altman (2009)
J. Immunol. 183, 1685-1694
   Abstract »    Full Text »    PDF »
Neuronal activity moves protein palmitoylation into the synapse.
M. B. Dalva (2009)
J. Cell Biol. 186, 7-9
   Abstract »    Full Text »    PDF »
Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95.
J. Noritake, Y. Fukata, T. Iwanaga, N. Hosomi, R. Tsutsumi, N. Matsuda, H. Tani, H. Iwanari, Y. Mochizuki, T. Kodama, et al. (2009)
J. Cell Biol. 186, 147-160
   Abstract »    Full Text »    PDF »
Differential palmitoylation of the endosomal SNAREs syntaxin 7 and syntaxin 8.
Y. He and M. E. Linder (2009)
J. Lipid Res. 50, 398-404
   Abstract »    Full Text »    PDF »
Lipid-Protein Interactions along the Slit Diaphragm of Podocytes.
B. Schermer and T. Benzing (2009)
J. Am. Soc. Nephrol. 20, 473-478
   Abstract »    Full Text »    PDF »
Palmitoylation of Cytoskeleton Associated Protein 4 by DHHC2 Regulates Antiproliferative Factor-mediated Signaling.
S. L. Planey, S. K. Keay, C.-O. Zhang, and D. A. Zacharias (2009)
Mol. Biol. Cell 20, 1454-1463
   Abstract »    Full Text »    PDF »
2-Bromopalmitate and 2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one inhibit DHHC-mediated palmitoylation in vitro.
B. C. Jennings, M. J. Nadolski, Y. Ling, M. B. Baker, M. L. Harrison, R. J. Deschenes, and M. E. Linder (2009)
J. Lipid Res. 50, 233-242
   Abstract »    Full Text »    PDF »
An All-Purpose Tool for Axon Guidance.
L. C. Schecterson and M. Bothwell (2008)
Science Signaling 1, pe50
   Abstract »    Full Text »    PDF »
CSS-Palm 2.0: an updated software for palmitoylation sites prediction.
J. Ren, L. Wen, X. Gao, C. Jin, Y. Xue, and X. Yao (2008)
Protein Eng. Des. Sel. 21, 639-644
   Abstract »    Full Text »    PDF »
Rapid detection, discovery, and identification of post-translationally myristoylated proteins during apoptosis using a bio-orthogonal azidomyristate analog.
D. D. O. Martin, G. L. Vilas, J. A. Prescher, G. Rajaiah, J. R. Falck, C. R. Bertozzi, and L. G. Berthiaume (2008)
FASEB J 22, 797-806
   Abstract »    Full Text »    PDF »
Identification of palmitoylated mitochondrial proteins using a bio-orthogonal azido-palmitate analogue.
M. A. Kostiuk, M. M. Corvi, B. O. Keller, G. Plummer, J. A. Prescher, M. J. Hangauer, C. R. Bertozzi, G. Rajaiah, J. R. Falck, and L. G. Berthiaume (2008)
FASEB J 22, 721-732
   Abstract »    Full Text »    PDF »
Control of Inward Rectifier K Channel Activity by Lipid Tethering of Cytoplasmic Domains.
D. Enkvetchakul, I. Jeliazkova, J. Bhattacharyya, and C. G. Nichols (2007)
J. Gen. Physiol.
   Abstract »    Full Text »    PDF »
Cellular palmitoylation and trafficking of lipidated peptides.
J. M. Draper, Z. Xia, and C. D. Smith (2007)
J. Lipid Res. 48, 1873-1884
   Abstract »    Full Text »    PDF »
Seven-Transmembrane Receptors and Ubiquitination.
S. K. Shenoy (2007)
Circ. Res. 100, 1142-1154
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882