Abstract
As illustrated in Fig. 1, the binding of a hormone (H), neurotransmitter or growth factor to a receptor (R) in a membrane can activate a phosphoinositide-specific phospholipase C (PLC) that hydrolyzes phosphatidylinositol 4,5-bisphosphate (PEP2) into the two second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses through the cytoplasm and releases calcium ions from the endoplasmic reticulum (ER). The increase in the cytoplasmic concentration of Ca++ produces translocation of protein kinase C (PKC) to the plasma membrane and concomitant activation of this enzyme. Maximal activation of PKC requires DAG, which remains in the membrane, and an acidic lipid such as phosphatidylserine (PS). The requirement for PS suggests that basic residues on the protein (+ signs) interact with acidic lipids in the membrane. The membrane-bound, activated form of PKC then phosphorylates its membrane-bound substrates, which include the myristoylated alanine-rich C kinase substrate (MARCKS) and pp60src (Src).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Adam, G. and Delbruck, M. (1968) Reduction of dimensionality in biological diffusion processes. In: Structural Chemistry and Molecular Biology, edited by A. Rich and N. Davidson. San Francisco: W.H. Freeman and Company, p. 198–215.
Aderem, A. (1992) The MARCKS brothers: a family of protein kinase C substrates. Cell 71:713–716.
Berridge, M.J. (1993) Inositol trisphosphate and calcium signalling. Nature 361:315–325.
Blackshear, P.J. (1993) The MARCKS family of cellular protein kinase C substrates. J. Biol. Chem. 268:1501–1504.
Buser, C.A., Sigal, C.T., Resh, M.D., and McLaughlin, S. (1994) Membrane binding of myristylated peptides corresponding to the NH2-terminus of Src. Biochemistry 33:13093–13101.
Carpenter, G. (1992) Receptor tyrosine kinase substrates: src homology domains and signal transduction. FASEBJ. 6:3283–3289.
Cifuentes, M.E., Honkanen, L., and Rebecchi, M.J. (1993) Proteolytic fragments of phosphoinositide-specific phospholipase C-dj. Catalytic and membrane binding properties. J. Biol Chem. 268:11586–11593.
Cohen, G.B., Ren, R, and Baltimore, D. (1995) Modular binding domains in signal transduction proteins. Cell 80:237–248.
Davis, M.E. and McCammon, J.A. (1990) Electrostatics in biomolecular structure and dynamics. Chem. Rev. 90:509–521.
Ferguson, K.M., Lemmon, M.A., Schlessinger, J., and Sigler, P.B. (1994) Crystal structure at 2.2 A resolution of the pleckstrin homology domain from human dynamin. Cell 79:199–209.
Garcia, P., Gupta, R., Shah, S., Morris, A.J., Rudge, S.A., Scarlata, S., Petrova, V., McLaughlin, S., and Rebecchi, M.J. (1995) Binding of the pleckstrin homology domain of phospholipase C-6l to membrane bilayers and inositol 1,4,5-trisphosphate. Biochemistry submitted.
Gibson, T.J., Hyvonen, M., Musacchio, A., Saraste, M., and Birney, E. (1994) PH domain: the first anniversary. Trends Biochem. Sci. 19:349–353.
Harlan, J.E., Hajduk, P.J., Yoon, H.S., and Fesik, S.W. (1994) Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature 371:168–170.
Harlan, J.E., Yoon, H.S., Hajduk, P.J., and Fesik, S.W. (1995) Structural characterization of the interaction between a pleckstrin homology domain and phosphatidylinositol 4,5-bisphosphate. Biochemistry 34:9859–9864.
Haslam, R.J., Kolde, H.B., and Hemmings, B.A. (1993) Pleckstrin domain homology. Nature 363:309–310.
Jahnig, F. (1976) Electrostatic free energy and shift of the phase transition for charged lipid membranes. Biophys. Chem. 4:309–318.
Jain, M.K. and Berg, O.G. (1989) The kinetics of interfacial catalysis by phospholipase A2 and regulation of interfacial activation: hopping versus scooting. Biochim. Biophys. Acta 1002:127–156.
James, G. and Olson, E.N. (1989) Myristoylation, phosphorylation, and subcellular distribution of the 80-kDa protein kinase C substrate in BC3H1 myocytes. J. Biol. Chem. 264: 20928–20933.
James, S.R., Paterson, A., Harden, T.K., and Downes, C.P. (1995) Kinetic analysis of phospholipase Cp isoforms using phospholipid-detergent mixed micelles. Evidence for interfacial catalysis involving distinct micelle binding and catalytic steps. J. Biol. Chem. 270:11872–11881.
Kim, J., Blackshear, P.J., Johnson, J.D. and McLaughlin, S. (1994a) Phosphorylation reverses the membrane association of peptides that correspond to the basic domains of MARCKS and neuromodulin. Biophys. J. 67:227–237.
Kim, J., Shishodo, T., Jiang, X., Aderem, A., and McLaughlin, S. (1994b) Phosphorylation, high ionic strength, and calmodulin reverse the binding of MARCKS to phospholipid vesicles. J. Biol. Chem. 269:28214–28219.
Lee, S.B., and Rhee, S.G. (1995) Significance of PIP2 hydrolysis and regulation of phospholipase C isozymes. Cur. Opin . Cell Biol. 7:183–189.
Macias, M.J., Musacchio, A., Ponstingl, H., Nilges, M., Saraste, M., and Oschkinat H. (1994) Structure of the pleckstrin homology domain from beta-spectrin.Nature 369:675–677.
McLaughlin, S. (1989) The electrostatic properties of membranes. Annu. Rev. Biophys. Biophys. Chem. 18:113–136.
McLaughlin, S. and Aderem, A. (1995) The myristoyl-electrostatic switch: A modulator of reversible protein-membrane interactions. Trends Biochem. Sci. 20:272–276.
Montich, G., Scarlata, S., McLaughlin, S., Lehrmann, R., and Seelig, J. (1993) Thermodynamic characterization of the association of small basic peptides with membranes containing acidic lipids. Biochim. Biophys. Acta 1146:17–24.
Mosior, M. and McLaughlin, S. (1991) Peptides that mimic the pseudosubstrate region of protein kinase C bind to acidic lipids in membranes. Biophys J. 60:149–159.
Newton, A.C. (1993) Interaction of proteins with lipid headgroups: lessons from protein kinase C. Annu. Rev. Biophys. Biomol. Structure 22:1–25.
Op denKamp, J.A. (1979) Lipid asymmetry in membranes. Annu. Rev. Biochem. 48:47–71.
Parker, P.J., Hemmings, B.A., and Gierschik, P. (1994) PH domains and phospholipases — a meaningful relationship?. Trends Biochem. Sci. 19:54–55.
Parsegian, A. (1969) Energy of an ion crossing a low dielectric membrane; solutions to four relevant electrostatic problems. Nature 221:844–846.
Pawelczyk, T., and Lowenstein, J.M. (1993) Binding of phosholipase C-Sj to phospholipid vesicles. Biochem. J. 291:693–696.
Pawson, T. (1995) Protein modules and signalling networks. Nature 373:573–580.
Peitzsch, R.M., Eisenberg, M., Sharp, K.A., and McLaughlin, S. (1995) Calculations of the electrostatic potential adjacent to model phospholipid bilayers. Biophys. J. 68:729–738.
Peitzsch, R.M. and McLaughlin, S. (1993) Binding of acylated peptides and fatty acids to phospholipid vesicles: pertinence to myristoylated proteins. Biochemistry 32:10436–10443.
Pitcher,J.A., Touhara,K., Payne,E.S., and Lefkowitz,R.J. (1995) Pleckstrin homology domainmediated membrane association and activation of the p-adrenergic receptor kinase requires coodinate interaction with G Py subunits and lipid. J. Biol. Chem. 270:11707–11710.
Raudino, A. (1995) Lateral inhomogeneous lipid membranes: theoretical aspects. Adv. Colloid Interfac. Sci. 57:229–285.
Rebecchi, M.,Peterson,A., and McLaughlin, S. (1992) Phosphoinositide-specific phospholipase C-6X binds with high affinity to phospholipid vesicles containing phosphatidylinositol 4,5-bisphosphate. Biochemistry 31:12742–12747.
Resh, M.D. (1993) Interaction of tyrosine kinase oncoproteins with cellular membranes. Biochim. Biophys. Acta 1155:307–322.
Rhee, S.G. and Choi, K.D. (1992) Regulation of inositol phospholipid-specific phospholipase C isozymes. J. Biol Chem. 267:12393–12396.
Rosen, A., Keenan, K.F., Thelen, M., Nairn, A.C., and Aderem, A. (1990) Activation of protein kinase C results in the displacement of its myristoylated, alanine-rich substrate from punctate structures in macrophage filopodia. J. Exp. Med. 172:1211–1215.
Roux, M., Neumann, J.M., Bloom, M., and Devaux, P.F. (1988) 2H and 31P NMR study of pentalysine interaction with headgroup deuterated phosphatidylcholine and phosphatidylserine. Eur. Biophys. J. 16:267–273.
Sharp, K.A. and Honig, B.H. (1990) Electrostatic interactions in macromolecules: theory and applications. Annu. Rev. Biophys. Biophys. Chem. 19:301–332.
Sigal, C.T., Zhou, W., Buser, C.A., McLaughlin, S., and Resh, M.D. (1994) The amino terminal basic residues of Src mediate membrane binding through electrostatic interaction with acidic phospholipids. Proc. Natl. Acad. Sci. U.S.A. 91:12253–12257.
Silvius, J.R. and l’Heureux, F. (1994) Fluorimetric evaluation of the affinities of isoprenylated peptides for lipid bilayers. Biochemistry 33:3014–3022.
Sternweis, P.C. and Smrcka, A.V. (1992) Regulation of phospholipase C by G proteins. Trends Biochem. Sci. 17:502–506.
Sutton, R.B., Davletov, B.A., Berghuis, A.M., Sudhof, T.C., and Sprang, S.R. (1995) Structure of the first C2 domain of synaptotagmin I: A novel Ca27phospholipid-binding fold. Cell 80:929–938.
Tanford, C. (1991) The Hydrophobic Effect: Formation of Micelles and Biological Membranes. Malabar, FL: Krieger Publishing Co.
Taniguchi, H. and Manenti, S. (1993) Interaction of myristoylated alanine-rich protein kinase C substrate (MARCKS) with membrane phospholipids. J. Biol. Chem. 268:9960–9963.
Thelen, M., Rosen, A., Nairn, AC., and Aderem, A. (1991) Regulation by phosphorylation of reversible association of a myristoylated protein kinase C substrate with the plasma membrane. Nature 351:320–322.
Towler, D.A., Gordon, J.I., Adams, S.P., and Glaser, L. (1988) The biology and enzymology of eukaryotic protein acylation. Annu. Rev. Biochem. 57:69–99.
Trauble, H. (1977) Membrane electrostatics. In: Structure of Biological Membranes. Edited by S. Abrahamsson and I. Pascher. New York: Plenum Press, p. 509–550.
Trauble, H., Teubner, M., Woolley, P., and Eibl, H. (1976) Electrostatic interactions at charged lipid membranes. I. Effects of pH and univalent cations on membrane structure. Biophys. Chem. 4:319–342.
Vergeres, G., Manenti, S., and Weber, T. (1995) Interaction of MARCKS, a major protein kinase C substrate, with the membrane. In: Signalling Mechanisms: From Transcription Factors to Oxidative Stress, edited by L. Packer and K. Wirtz. NATO ASI Series. Berlin: Springer-Verlag.
Wang, J. K, Walaas, S.I., Sihra, T.S., Aderem, A., and Greengard, P. (1989) Phosphorylation and associated translocation of the 87-kDa protein, a major protein kinase C substrate, in isolated nerve terminals. Proc. Natl. Acad. Sci. U.S.A. 86:2253–2256.
Wedegaertner, P.B., Wilson, P.T., and Bourne, H.R. (1995) Lipid modifications of trimeric G proteins. J. Biol. Chem. 270:503–506.
Yang, L. and Glaser, M. (1995) Membrane domains containing phosphatidylserine and substrate can be important for the activation of protein kinase C. Biochemistry 34:1500–1506.
Yoon, H.S., Hajduk, P.J., Petros, A.M., Olejniczak, E.T., Meadows, R.P., and Fesik, S.W. (1994) Solution structure of a pleckstrin-homology domain. Nature 369:672–675.
Zheng, J., Knighton, D. R, Xuong, N.H., Taylor, S.S., Sowadski, J.M., and Ten Eyck, L.F. (1993) Crystal structures of the myristylated catalytic subunit of cAMP-dependent protein kinase reveal open and closed conformations. Protein Science 2:1559–1573.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
McLaughlin, S. et al. (1996). The Importance of Lipid-Protein Interactions in Signal Transduction Through the Calcium-Phospholipid Second Messenger System. In: Op den Kamp, J.A.F. (eds) Molecular Dynamics of Biomembranes. NATO ASI Series, vol 96. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61126-1_19
Download citation
DOI: https://doi.org/10.1007/978-3-642-61126-1_19
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64707-9
Online ISBN: 978-3-642-61126-1
eBook Packages: Springer Book Archive