The proteins of the MARCKS (myristoylated alanine-rich C kinase substrate) family were first identified as prominent substrates of protein kinase C (PKC). Since then, these proteins have been implicated in the regulation of brain development and postnatal survival, cellular migration and adhesion, as well as endo-, exo- and phago-cytosis, and neurosecretion. The effector domain of MARCKS proteins is phosphorylated by PKC, binds to calmodulin and contributes to membrane binding. This multitude of mutually exclusive interactions allows cross-talk between the signal transduction pathways involving PKC and calmodulin. This review focuses on recent, mostly biophysical and biochemical results renewing interest in this protein family. MARCKS membrane binding is now understood at the molecular level. From a structural point of view, there is a consensus emerging that MARCKS proteins are ‘natively unfolded'. Interestingly, domains similar to the effector domain have been discovered in other proteins. Furthermore, since the effector domain enhances the polymerization of actin in vitro, MARCKS proteins have been proposed to mediate regulation of the actin cytoskeleton. However, the recent observations that MARCKS might serve to sequester phosphatidylinositol 4,5-bisphosphate in the plasma membrane of unstimulated cells suggest an alternative model for the control of the actin cytoskeleton. While myristoylation is classically considered to be a co-translational, irreversible event, new reports on MARCKS proteins suggest a more dynamic picture of this protein modification. Finally, studies with mice lacking MARCKS proteins have investigated the functions of these proteins during embryonic development in the intact organism.
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Review Article|
February 08 2002
Cross-talk unfolded: MARCKS proteins
Anna ARBUZOVA
;
Anna ARBUZOVA
∗Department of Physiology and Biophysics, Health Sciences Center, State University of New York, Stony Brook, NY 11794-8661, U.S.A.
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Arndt A. P. SCHMITZ
;
Arndt A. P. SCHMITZ
1
†Department of Biophysical Chemistry, Biozentrum, Universität Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland
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Guy VERGÈRES
Guy VERGÈRES
2
‡Preclinical Development, ZLB Bioplasma AG, Wankdorfstr. 10, CH-3000 Bern 22, Switzerland
2To whom correspondence should be addressed (e-mail guy.vergeres@zlb.com).
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Biochem J (2002) 362 (1): 1–12.
Citation
Anna ARBUZOVA, Arndt A. P. SCHMITZ, Guy VERGÈRES; Cross-talk unfolded: MARCKS proteins. Biochem J 15 February 2002; 362 (1): 1–12. doi: https://doi.org/10.1042/bj3620001
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