Reversible palmitoylation of signaling proteins

Current Opinion in Cell Biology

Volumn 9, Issue 2, 1997, Pages 148-154

  Mumby, Susanne M ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; GUANINE NUCLEOTIDE BINDING PROTEIN; MEMBRANE PROTEIN;

CELL MEMBRANE; ENZYME ACTIVITY; ENZYME PURIFICATION; PALMITOYLATION; PRIORITY JOURNAL; PROTEIN LIPID INTERACTION; PROTEIN LOCALIZATION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

EID: 0030936823     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(97)80056-7     Document Type: Article

References (60)

1. Mllligan G, Parenti M, Magee AI: The dynamic role of palmitoylation in signal transduction. Trends Biochem Sci 1995, 20:181-186.
2. Mollner S, Becl K, Pfeuffer T: Acylation of adenylyl cyclase catalyst is important for enzymic activity. FEBS Lett 1995, 371:241-244.
3. Ross EM: Palmitoylation in G-protein signaling pathways. Curr Biol 1995, 5:107-109.
4. Hallak H, Muszbek L, Laposata M, Belmonte E, Brass LF, Manning DR: Covalent binding of arachidonate to G protein α subunits of human platelets. J Biol Chem 1994, 269:4713-4716.
5. Fujimoto T, Stroud E, Whatley RE, Prescott SM, Muszbek L, Laposata M, McEver RP: P-selectin is acylated with palmitic acid and stearic acid at cysteine 766 through a thioester linkage. J Biol Chem 1993, 268:11394-11400.
6. Nadler MJ, Hu XE, Cassady JM, Geahlen RL: Posttranslational acylation of the transferrin receptor in LSTRA cells with myristate, palmitate and stearate: evidence for distinct acyltransferases. Biochim Biophys Acta 1994, 1213:100-106.
7. Mouillac B, Caron M, Bonin H, Dennis M, Bouvier M: Agonist-modulated palmitoylation of β2-adrenergic receptor in Sf9 cells. J Biol Chem 1992. 267:21733-21737.
8. sα. Cell 1994, 77:1063-1070.
9. Mumby SM, Kleuss C, Gilman AG: Receptor regulation of G protein palmitoylation. Proc Natl Acad Sci USA 1994, 91:2800-2804.
10. s protein α subunit after activation by the β-adrenergic receptor or cholera toxin. J Biol Chem 1993, 268:23769-23772.
11. Robinson LJ, Busconi L, Michel T: Agonist-modulated palmitoylation of endothelial nitric oxide synthase. J Biol Chem 1995, 270:995-998.
12. Liu J, Garcia-Cardena G, Sessa WC: Biosynthesis and palmitoylation of endothelial nitric oxide synthase: mutagenesis of palmitoylation sites, cysteines-15 and/or-26, argues against depalmitoylation-induced translocation of the enzyme. Biochemistry 1995, 34:12333-12340.
13. Paige LA, Nadler MJS, Harrison ML, Cassady JM, Geahlen RL: Reversible palmitoylation of the protein-tyrosine kinase p56(lck). J Biol Chem 1993, 268:8669-8674.
14. Peitzsch RM, McLaughlin S: Binding of acylated peptides and fatty acids to phospholipid vesicles - pertinence to myristoylated proteins. Biochemistry 1993, 32:10436-10443.
15. Anderson RGW: Caveolae: where incoming and outgoing messengers meet Proc Natl Acad Sci USA 1993, 90:10909-10913.
16. Lisanti MP, Scherer PE, Tang Z, Sargiacomo M: Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis. Trends Cell Biol 1994, 4:231-235.
17. Parton RG, Simons K: Digging into caveolae. Science 1995, 269:1398-1399.
18. Chang W-J, Ying Y-S, Rothberg KG, Hooper NM, Turner AJ, Gambliel HA, De Gunzburg J, Mumby SM, Gilman AG, Anderson RGW: Purification and characterization of smooth muscle cell caveolae. J Cell Biol 1994, 126:127-138.
19. Sargiacomo M, Sudol M, Tang ZL, Lisanti MP: Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J Cell Biol 1993, 122:789-807.
20. Smart EJ, Ying Y-S, Mineo C, Anderson RGW: A detergent-free method for purifying caveolae membrane from tissue culture cells. Proc Natl Acad Sci USA 1995, 92:10104-10108.
21. Song KS, Li S, Okamoto T, Quilliam LA, Sargiacomo M, Lisanti MP: Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. J Biol Chem 1996, 271:9690-9697.
22. Mineo C, James GL, Smart EJ, Anderson RGW: Localization of epidermal growth factor-stimulated Ras/Raf-1 interaction to caveolae membrane. J Biol Chem 1996, 271:11930-11935.
23. Shenoy-Scaria AM, Dietzen DJ, Kwong J, Link DC, Lublin DM: Cysteine(3) of Src family protein tyrosine kinases determines palmitoylation and localization in caveolae. J Cell Biol 1994, 126:353-363.
24. Robbins SM, Quintrell NA, Bishop JM: Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae. Mol Cell Biol 1995, 15:3507-3515.
25. Rodgers W, Crise B, Rose JK: Signals determining protein tyrosine kinase and glycosyl-phosphatidylinositol-anchored protein targeting to a glycolipid-enriched membrane fraction. Mol Cell Biol 1994, 14:5384-5391.
26. Shaul PW, Smart EJ, Robinson LJ, German Z, Yuhanna IS, Ying Y, Anderson RGW, Michel T: Acylation targets endothelial nitric-oxide synthase to plasmalemmal caveolae. J Biol Chem 1996, 271:6518-6522. Endogenous eNOS is found, by fractionation and immunoelectron microscopic techniques, to be localized to caveolae. Wild-type eNOS ectopically expressed in transfected COS cells cofractionates with caveolin. The non-palmitoylated mutant protein, which is membrane-associated, is not enriched in the caveolar fractions of transfected cells. The Cys sites of palmitoylation in eNOS are, therefore, necessary for the cofractionation of the enzyme with caveolar membranes. These results are consistent with those in [27••].
27. Garcia-Cardena G, Oh P, Liu J, Schnitzer JE, Sessa WC: Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. Proc Natl Acad Sci USA 1996. 93:6448-6453. Endogenous eNOS cofractionates with caveolin. Double immunofluorescence experiments reveal that wild-type eNOS, expressed ectopically in 3T3 cells by transfection, colocalizes with caveolin at the plasma membrane. The double Cys mutant protein, which cannot be palmitoylated, does not colocalize with caveolin at the plasma membrane but is instead detected in the perinuclear region and diffusely throughout the cytoplasm. The two Cys sites of palmitoylation in eNOS are, therefore, necessary for the colocalization of eNOS and caveolin. These results are consistent with those in [26••].
28. Rothberg KG, Heuser JE, Donzell WC, Ying Y-S, Glenney JR, Anderson RGW: Caveolin, a protein component of caveolae membrane coats. Cell 1992, 68:673-682.
29. Muntz KH: β-ARs in caveolae? Trends Cell Biol 1994, 4:354.
30. Lisanti MP: β-ARs in caveolae? Reply. Trends Cell Biol 1994, 4:354.
31. Slezak J, Geller SA: Cytochemical studies of myocardial adenylate cyclase after its activation and inhibition. J Histochem Cytochem 1984, 32:105-113.
32. Rechardt L, Hervonen H: Cytochemical demonstration of adenylate cyclase activity with cerium. Histochemistry 1985, 82:501-505.
33. Robinson U, Michel T: Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc Natl Acad Sci USA 1995, 92:11776-11780.
34. sα to caveolar-like membranes.
35. Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP: Identification, sequence, and expression of caveolin-2 defines a caveolin gene family. Proc Natl Acad Sci USA 1996, 93:131-135.
36. Tang Z, Scherer PE, Okamoto T, Song K, Chu C, Kohtz DS, Nishimoto I, Lodish HF, Lisanti MP: Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle. J Biol Chem 1996, 271:2255-2261.
37. Rodbell M: Programmable messengers: a new theory of hormone action. Trends Biochem Sci 1985, 10:461-464.
38. s protein in native membranes. J Biol Chem 1988, 263:17239-17242.
39. s in intact cells alters its abundance, rate of degradation, and membrane avidity. J Cell Biol 1992, 119:1297-1307.
40. sα. Mol Biol Cell 1996, 7:1225-1233.
41. sα. J Biol Chem 1993, 268:25001-25008.
42. qα, regardless of their palmitoylation state, are necessary for activation of phospholipase C. This study highlights the fact that a phenotype associated with the mutation of Cys residues cannot be directly attributed to the lack of palmitate. We are reminded that Cys residues themselves, rather than the lack of palmitate, can contribute to the losses in signal transduction that are observed in transfected cell systems such as those described in [41,43].
43. qα is required for coupling to the NK2 receptor. FEBS Lett 1994, 354:194-199.
44. Kuroda Y, Suzuki N, Kataoka T: The effect of posttranslational modifications on the interaction of Ras2 with adenylyl cyclase. Science 1993, 259:683-686.
45. sα and its nonpalmitoylated counterpart were compared di-rectly without need for mutation. Palmitoylation increased the affinity of Gα for Gβγ by a factor of five. Heterotrimeric protein is more resistant than α subunit alone to the effects of a palmitoyl transferase.
46. Jackson CS, Zlatkine P, Bano C, Kabouridis P, Mehul B, Parenti M, Milligan G, Ley SC, Magee AI: Dynamic protein acylation and the regulation of localization and function of signal-transducing proteins. Biochem Soc Trans 1995, 23:568-571.
47. Liu L, Dudler T, Gelb MH: Purification of a protein palmitoyltransferase that acts on H-Ras protein and on a C-terminal N-Ras peptide. J Biol Chem 1996, 271:23269-23276. Enzymes with protein palmitoyl acyltransferase activity have been notoriously recalcitrant to purification. This paper describes the first successful purification of such an enzyme. It will be exciting to learn what role this enzyme may play in the cellular regulation of protein palmitoylation.
48. Berthiaume L, Resh MD: Biochemical characterization of a palmitoyl acyltransferase activity that palmitoylates myristoylated proteins. J Biol Chem 1995, 270:22399-22405. Identification and characterization of protein palmitoyl acyltransferase activity for a nonreceptor-kinase substrate is described. This transferase enzyme activity exhibits less stringent requirements in acyl-CoA chain length than does the Ras-palmitoylating enzyme in [47••]. The preference for myristoylated polypeptide and long-chain acyl-CoA substrates is similar to that reported in [49•].
49. Dunphy JT, Greentree WK, Manahan CL, Linder ME: G protein palmitoyltransferase activity is enriched in plasma membranes. J Biol Chem 1996, 271:7154-7159. The identification and biochemical characterization of a protein palmitoyl acyltransferase activity for G-protein subunits is described. The preference for myristoylated polypeptide and long-chain acyl-CoA substrates is similar to that reported in [48•].
50. Duncan JA, Gilman AG: Autoacylation of G protein α subunits. J Biol Chem 1996, 271:23594-23600. In vitro transfer of the palmitoyl group from palmitoyl-CoA to Cys residues of G-protein subunits occurs readily without the addition of an enzyme source. Many of the characteristics of the autoacylation are astonishingly similar to those observed for palmitoylation of α subunits in vivo and in the in vitro enzyme-catalyzed reaction described in [49•]. The autoacylation reaction is, however, typically performed at much higher palmitoyl-CoA concentrations.
51. Camp LA, Verkruyse LA, Afendis SJ, Slaughter CA, Hofmann SL: Molecular cloning and expression of palmitoyl-protein thioesterase. J Biol Chem 1994, 269:23212-23219.
52. Verkruyse LA, Hofmann SL: Lysosomal targeting of palmitoylprotein thioesterase. J Biol Chem 1996, 271:15831-15836.
53. Sleat DE, Lackland SI, Majercak J, Lobel P: Rat brain contains high levels of mannose-6-phosphorylated glycoproteins including lysosomal enzymes and palmitoyl-protein thioesterase, an enzyme implicated in infantile neuronal lipofuscinosis. J Biol Chem 1996, 271:19191-19198.
54. Hellsten E, Vesa J, Olkkonen VM, Jalanko A, Peltonen L: Human palmitoyl protein thioesterase: evidence of lysosomal targeting of the enzyme and disturbed cellular routing in infantile neuronal ceroid lipofuscinosis. EMBO J 1996, 19:5240-5245.
55. 11α in defining interaction with the plasma membrane. Biochem J 1995, 310:1021-1027
56. ssubunit incorporates [3H]palmitic acid and mutation of cysteine-3 prevents this modification. Biochemistry 1993, 32:8057-8061.
57. i subunit requires membrane localization not myristoylation. J Biol Chem 1995, 269:30898-30903.
58. fyn affects subcellular localization. J Biol Chem 1994, 269:16701-16705.
59. Hancock JF, Magee AI, Childs JE, Marshall CJ: All ras proteins are polyisoprenylated but only some are palmitovlated. Cell 1989, 57:1167-1177.
60. Neer EJ, Clapham DE: Roles of G protein subunits in transmembrane signalling. Nature 1988, 333:129-134.