The intracellular form of human MAGP1 elicits a complex and specific transcriptional response.
Microfibril-associated glycoprotein-1 (MAGP1) is found associated with microfibrils in the extracellular matrix (ECM). In humans, MAGP1 is expressed as two alternatively spliced isoforms: MAGP1A, the extracellular microfibril-associated form; and MAGP1B, an exclusively intracellular isoform derived from the skipping of exon 3. The biological function of MAGP1B is unknown. We performed gene expression profiling to study the cellular response to MAGP1B using whole-genome genechips. We found that MAGP1B specifically induces the expression of genes linked to cell adhesion, motility, metabolism, gene expression, development and signal transduction. Versican, a gene product involved in the structure and functional regulation of the ECM, showed the highest up-regulation in response to MAGP1B. These studies suggest a dual role for MAGP1, with extracellular MAGP1A involved in ECM function, and intracellular MAGP1B modulating the expression of genes that function in cell adhesion, migration and control of ECM deposition.
Segade
Fernando
F
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. segade@dental.upenn.edu
Suganuma
Nobuyasu
N
Mychaleckyj
Josyf C
JC
Mecham
Robert P
RP
D045744:Cell Line, Tumor; D039241:Cleavage Stimulation Factor; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020555:GTP-Binding Protein Regulators / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039441:Integrin alpha4 / Q000235:genetics; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D000072079:Patched Receptors; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection; D053675:Versicans / Q000235:genetics
C484093:CDC42EP3 protein, human; C474466:CSTF2T protein, human; D039241:Cleavage Stimulation Factor; D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins; D020555:GTP-Binding Protein Regulators; D000072079:Patched Receptors; D020033:Protein Isoforms; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C508322:VCAN protein, human; C016598:microfibrillar protein; D053675:Versicans; D039441:Integrin alpha4
Bioessays. 1991 Oct;13(10):527-33
1755828
Science. 1991 Aug 16;253(5021):802
1678898
J Biol Chem. 1993 Dec 25;268(36):27381-9
8262979
Matrix. 1993 Nov;13(6):457-69
8309425
J Biol Chem. 1994 Nov 11;269(45):28443-9
7961786
Genomics. 1995 Feb 10;25(3):630-7
7759096
Bone. 1995 Apr;16(4):415-26
7605701
J Biol Chem. 1996 Mar 1;271(9):4916-22
8617764
J Biol Chem. 1997 Sep 5;272(36):22817-23
9278443
Mol Cell Biol. 1999 Oct;19(10):6585-97
10490598
Gene. 2005 Jan 3;344:1-20
15656968
Mol Biol Cell. 2005 Mar;16(3):1330-40
15635104
Int J Cancer. 2005 May 10;114(6):879-86
15645431
J Clin Invest. 2005 Jun;115(6):1542-51
15902308
Regul Pept. 2006 Jan 15;133(1-3):1-9
16226324
J Biol Chem. 2006 Apr 14;281(15):10089-97
16492672
J Med Genet. 2000 Jan;37(1):9-25
10633129
Mol Biol Cell. 2000 May;11(5):1499-507
10793130
J Cell Biochem. 2000 Sep 14;79(4):576-82
10996848
Microsc Res Tech. 2000 Nov 1;51(3):214-27
11054872
Matrix Biol. 2000 Dec;19(7):671-82
11102756
Biochem J. 2000 Dec 15;352 Pt 3:601-10
11104663
J Biol Chem. 2001 Jan 12;276(2):875-83
11035016
Nat Cell Biol. 2001 Oct;3(10):861-6
11584266
J Biol Chem. 2002 Feb 8;277(6):3950-7
11723132
J Biol Chem. 2002 Feb 8;277(6):4565-72
11726670
Methods. 2001 Dec;25(4):402-8
11846609
Circ Res. 2002 Mar 8;90(4):481-7
11884379
J Biol Chem. 2002 Mar 29;277(13):11050-7
11796718
J Cell Biol. 2002 May 27;157(5):873-82
12021259
Mol Biol Cell. 2002 Sep;13(9):3203-17
12221126
Curr Opin Cell Biol. 2002 Oct;14(5):608-16
12231357
Curr Opin Cell Biol. 2002 Oct;14(5):617-23
12231358
Nucleic Acids Res. 2003 Jan 1;31(1):51-4
12519945
Nat Med. 2003 Sep;9(9):1158-65
12897778
Nucleic Acids Res. 2003 Dec 15;31(24):e154
14654707
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D258-61
14681407
Am J Pathol. 2004 Jan;164(1):119-31
14695326
Birth Defects Res C Embryo Today. 2004 Mar;72(1):37-50
15054903
J Biol Chem. 2004 May 28;279(22):23045-51
15044481
J Immunol. 2004 Nov 1;173(9):5659-70
15494517
J Natl Cancer Inst. 1977 Jul;59(1):221-6
327080
Anal Biochem. 1987 Apr;162(1):156-9
2440339
J Biol Chem. 1991 Apr 25;266(12):7596-601
2019589
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1403-7
1741396