The human myristoylated alanine-rich C kinase substrate (MARCKS) gene (MACS). Analysis of its gene product, promoter, and chromosomal localization.
AffiliationHoward Hughes Medical Institute Laboratories, Duke University Medical Center, Durham, North Carolina 27710.
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AbstractThe expression of a major cellular substrate for protein kinase C, the MARCKS protein, is regulated in a cell-, tissue-, and developmental stage-specific fashion; in addition, this expression can be stimulated acutely by various cytokines in certain cell types. We have begun to characterize the human gene in order to elucidate the genetic elements responsible for this highly regulated expression. We first cloned a human MARCKS cDNA, which encoded a predicted protein of 332 amino acids (Mr 31,600) that was approximately 89, 74, and 59% identical to the bovine, mouse, and chicken proteins, respectively. Regions conserved at the amino acid level included the amino-terminal myristoylation consensus sequence, the site of intron splicing, and the phosphorylation site domain. The human cDNA was used to demonstrate that tumor necrosis factor-alpha could rapidly stimulate MARCKS gene transcription in the human promyelocytic leukemia cell line HL60. Genomic clones were then isolated; sequence analysis identified a putative promoter region that had no TATA box and contained multiple transcription initiation sites in a region spanning 57 base pairs (bp). This was followed by a 5'-untranslated region of approximately 400 bp, which displayed a complex predicted secondary structure with a delta G of -73.4 kcal/mol. Plasmid constructions containing between 52 and 1453 bp of the human MARCKS promoter linked to the human growth hormone gene were then used in transient expression experiments. Constructions containing 52 and 110 bp of the MARCKS promoter did not exhibit promoter function while the larger constructions all exhibited promotor function; the 248-bp fragment of the MARCKS promoter was 80% as effective as the human ferritin promoter in stimulating expression of human growth hormone in intact cells. Using an insert from the human genomic clone as a probe, we identified human chromosome 6, q21-qter, as the location of the MARCKS gene; this has been assigned the gene symbol MACS.
CitationThe human myristoylated alanine-rich C kinase substrate (MARCKS) gene (MACS). Analysis of its gene product, promoter, and chromosomal localization. 1991, 266 (22):14399-405 J. Biol. Chem.
JournalJournal of Biological Chemistry
- Chromosomal mapping of the human (MACS) and mouse (Macs) genes encoding the MARCKS protein.
- Authors: Blackshear PJ, Tuttle JS, Oakey RJ, Seldin MF, Chery M, Philippe C, Stumpo DJ
- Issue date: 1992 Sep
- Promoter sequence, expression, and fine chromosomal mapping of the human gene (MLP) encoding the MARCKS-like protein: identification of neighboring and linked polymorphic loci for MLP and MACS and use in the evaluation of human neural tube defects.
- Authors: Stumpo DJ, Eddy RL Jr, Haley LL, Sait S, Shows TB, Lai WS, Young WS 3rd, Speer MC, Dehejia A, Polymeropoulos M, Blackshear PJ
- Issue date: 1998 Apr 15
- Molecular cloning, sequence, and expression of a cDNA encoding the chicken myristoylated alanine-rich C kinase substrate (MARCKS).
- Authors: Graff JM, Stumpo DJ, Blackshear PJ
- Issue date: 1989 Nov
- A mouse brain cDNA encodes a novel protein with the protein kinase C phosphorylation site domain common to MARCKS.
- Authors: Umekage T, Kato K
- Issue date: 1991 Jul 29
- Relationship between the major protein kinase C substrates acidic 80-kDa protein-kinase-C substrate (80K) and myristoylated alanine-rich C-kinase substrate (MARCKS). Members of a gene family or equivalent genes in different species.
- Authors: Herget T, Brooks SF, Broad S, Rozengurt E
- Issue date: 1992 Oct 1