Myristoylated alanine-rich C-kinase substrate is a protein that in humans is encoded by the MARCKSgene.[3][4][5]
It plays important roles in cell shape, cell motility, secretion, transmembrane transport, regulation of the cell cycle, and neural development.[6] Recently, MARCKS has been implicated in the exocytosis of a number of vesicles and granules such as mucin and chromaffin.
It is also the name of a protein family, of which MARCKS is the most studied member. They are intrinsically disordered proteins, with an acidic pH, with high proportions of alanine, glycine, proline, and glutamic acid. They are membrane-bound through a lipid anchor at the N-terminus, and a polybasic domain in the middle. They are regulated by Ca2+/calmodulin and protein kinase C. In their unphosphorylated form, they bind to actin filaments, causing them to crosslink, and sequester acidic membrane phospholipids such as PIP2.
The protein encoded by this gene is a substrate for protein kinase C. It is localized to the plasma membrane and is an actin filament crosslinking protein. Phosphorylation by protein kinase C or binding to calcium-calmodulin inhibits its association with actin and with the plasma membrane, leading to its presence in the cytoplasm. The protein is thought to be involved in cell motility, phagocytosis, membrane trafficking and mitogenesis.[5]
Interactions[]
MARCKS has been shown to interact with TOB1[7] and with NMT2.[8]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Hartwig JH, Thelen M, Rosen A, Janmey PA, Nairn AC, Aderem A (April 1992). "MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin". Nature. 356 (6370): 618–22. Bibcode:1992Natur.356..618H. doi:10.1038/356618a0. PMID1560845. S2CID4252140.
^Blackshear PJ (January 1993). "The MARCKS family of cellular protein kinase C substrates". The Journal of Biological Chemistry. 268 (3): 1501–4. PMID8420923.
^Prieto D, Zolessi FR (January 2017). "Functional Diversification of the Four MARCKS Family Members in Zebrafish Neural Development". Journal of Experimental Zoology Part B: Molecular and Developmental Evolution. 328 (1–2): 119–138. doi:10.1002/jez.b.22691. PMID27554589. S2CID13263249.
^Jin Cho S, La M, Ahn JK, Meadows GG, Joe CO (May 2001). "Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation". Biochemical and Biophysical Research Communications. 283 (2): 273–7. doi:10.1006/bbrc.2001.4773. PMID11327693.
Aderem A (August 1995). "The MARCKS family of protein kinase-C substrates". Biochemical Society Transactions. 23 (3): 587–91. doi:10.1042/bst0230587. PMID8566422.
Sakai K, Hirai M, Kudoh J, Minoshima S, Shimizu N (September 1992). "Molecular cloning and chromosomal mapping of a cDNA encoding human 80K-L protein: major substrate for protein kinase C". Genomics. 14 (1): 175–8. doi:10.1016/S0888-7543(05)80301-5. PMID1427823.
Harlan DM, Graff JM, Stumpo DJ, Eddy RL, Shows TB, Boyle JM, Blackshear PJ (August 1991). "The human myristoylated alanine-rich C kinase substrate (MARCKS) gene (MACS). Analysis of its gene product, promoter, and chromosomal localization". The Journal of Biological Chemistry. 266 (22): 14399–405. PMID1860846.
Graff JM, Stumpo DJ, Blackshear PJ (July 1989). "Characterization of the phosphorylation sites in the chicken and bovine myristoylated alanine-rich C kinase substrate protein, a prominent cellular substrate for protein kinase C". The Journal of Biological Chemistry. 264 (20): 11912–9. PMID2473066.
Taniguchi H, Manenti S, Suzuki M, Titani K (July 1994). "Myristoylated alanine-rich C kinase substrate (MARCKS), a major protein kinase C substrate, is an in vivo substrate of proline-directed protein kinase(s). A mass spectroscopic analysis of the post-translational modifications". The Journal of Biological Chemistry. 269 (28): 18299–302. PMID8034575.
Rao PH, Murty VV, Gaidano G, Hauptschein R, Dalla-Favera R, Chaganti RS (1994). "Subregional mapping of 8 single copy loci to chromosome 6 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 66 (4): 272–3. doi:10.1159/000133710. PMID8162705.
Taniguchi H, Manenti S (May 1993). "Interaction of myristoylated alanine-rich protein kinase C substrate (MARCKS) with membrane phospholipids". The Journal of Biological Chemistry. 268 (14): 9960–3. PMID8486722.
Jin Cho S, La M, Ahn JK, Meadows GG, Joe CO (May 2001). "Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation". Biochemical and Biophysical Research Communications. 283 (2): 273–7. doi:10.1006/bbrc.2001.4773. PMID11327693.