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The
name of this protein is derived from Myristoylated Alanine Rich
C Kinase Substrate as it was first identified as a major
substrate for protein kinase C (Aderem,
1992). MARKS is
present in neuronal tissue at 10mm
(Blackshear, 1993).
The protein becomes redistributed from the
cytoplasmic face of the plasma-membrane to the cytosol upon phosphorylation by
protein kinase C after stimulation of a number of cell types by a number of
agonists. More recently it has been discovered that MARCKS is a calcium/calmodulin
sensitive actin filament crosslinking protein, also controlled by
phosphorylation. The affinity of
the protein for actin is approximately halved upon phosphorylation. Weak
bundling activity is seen at high concentrations of MARCKS and this bundling
activity is also seen with a synthetic lysine rich peptide corresponding to
residues 155-173 of the protein. The actin binding region of MARKS (Hartwig
et al, 1992)
has been determined to be:- KRFSFKKSKLSGFSFKKN.
The role of MARCKS in cell spreading (Manenti
et al, 1997; Myat et
al, 1997; Yue et al, 2000), through
focal contact formation. MARCKS is found at the focal contacts of cultured cells.
MARCKS interacts with PIP2 (Rauch
et al, 2002),
and apparently sequesters it through non-specific electrostatic interaction (Wang
et al, 2002).
References:-
Aderem, A. (1992). Signal
transduction and the actin cytoskeleton: the roles of MARCKS and profilin. Trends
in Biochemistry 17, 438-443.
Blackshear, P.J.
(1993). J.Biol.Chem. 268, 1501-1504.
Disatnik, M.-H., Boutel, S. C., Lee, C. H.,
Mochy-Rosen, D. & Rando, T. A. (2002) Sequential activation of individual
PKC isozymes in integrin-mediated muscle cell spreading: a role for MARCKS in an
integrin signaling pathways. J.Cell Sci. 115, 2151-2163.
Hartwig, J. H., Thelen, M., Rosen, A., Janmey,
P. A., Nairn, A. C. & Aderem, A. (1992) Marcks is an actin filament
cross-linking protein regulated by protein-kinase-c and calcium calmodulin. Nature.
356, 618-622.
Manenti, S., Malecaze, F. & Darbon, J. M.
(1997) The major myritoylated PKC substrate (MARCKS) is involved in cell
spreading , tyrosine phosphorylation of paxillin, and focal contact formation. FEBS
letters. 419, 95-98.
Morash, S.C., Byers,
D.M. & Cook, H.W. (2000). Activation of phospholipase D by PKC and GTPgS
in human neuroblastoma cells overexpressing MARCKS. Biochim.Biophys.Acta.
1487, 177-189.
Myat, M. M., Anderson, S., Allen, L. A. &
Aderem, A. (1997) MARCKS regulates membrane ruffling and cell spreading. Curr.
Biol. 7, 611-614.
Rauch, M. E., Ferguson, C. G., Prestwich, G.
D. & Cafiso, D. S. (2002) Myristoylated alanine rich C kinase substrate (MARCKS)
sequesters spin-labeled phosphatidylinositol 4,5-bisphosphate in lipid bilayers.
J.Biol.Chem. 277, 14068-14076.
Wang, J., Gambhir, A., Hangyas-Mihalyne, G.,
Murray, D., Golebiewska, U. & McLaughlin, S. (2002) Lateral Sequestration of
Phosphatidylinositol 4,5-Bisphosphate by the Basic Effector Domain of
Myristoylated Alanine-rich C Kinase Substrate Is Due to Nonspecific
Electrostatic Interactions, J. Biol. Chem. 277, 34401-34412.
Yue, L., Lu, S., Garces,
J., Jin, T. & Li, J. (2000). Protein Kinase C-regulated dynamitin-macrophage-enriched
Myristolyated Alanine-Rich C Kinase Substrate interaction is involved in
macrophage cell spreading. J.Biol.Chem. 275, 23948-23956.
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