Goodpasture antigen-binding protein is a soluble exportable protein that interacts with type IV collagen. Identification of novel membrane-bound isoforms.
Goodpasture-antigen binding protein (GPBP) is a nonconventional Ser/Thr kinase for basement membrane type IV collagen. Various studies have questioned these findings and proposed that GPBP serves as transporter of ceramide between the endoplasmic reticulum and the Golgi apparatus. Here we show that cells expressed at least two GPBP isoforms resulting from canonical (77-kDa) and noncanonical (91-kDa) mRNA translation initiation. The 77-kDa polypeptide interacted with type IV collagen and localized as a soluble form in the extracellular compartment. The 91-kDa polypeptide and its derived 120-kDa polypeptide associated with cellular membranes and regulated the extracellular levels of the 77-kDa polypeptide. A short motif containing two phenylalanines in an acidic tract and the 26-residue Ser-rich region were required for efficient 77-kDa polypeptide secretion. Removal of the 26-residue Ser-rich region by alternative exon splicing rendered the protein cytosolic and sensitive to the reduction of sphingomyelin cellular levels. These and previous data implicate GPBPs in a multicompartmental program for protein secretion (i.e. type IV collagen) that includes: 1) phosphorylation and regulation of protein molecular/supramolecular organization and 2) interorganelle ceramide trafficking and regulation of protein cargo transport to the plasma membrane.
Revert
Fernando
F
Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain.
Ventura
Ignacio
I
Martínez-Martínez
Pilar
P
Granero-Moltó
Froilán
F
Revert-Ros
Francisco
F
Macías
Jesús
J
Saus
Juan
J
D000143:Acids / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D024141:Collagen Type IV / Q000737:chemistry*; D005091:Exons; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D010649:Phenylalanine / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism
D000143:Acids; D024141:Collagen Type IV; D020033:Protein Isoforms; D012333:RNA, Messenger; D010649:Phenylalanine; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases
J Lipid Res. 2007 Jun;48(6):1293-304
17392267
Biochem J. 2000 Oct 1;351(Pt 1):19-31
11001876
J Biol Chem. 2002 Aug 16;277(33):29908-18
12023275
J Biol Chem. 2006 Oct 6;281(40):30279-88
16895911
FEBS J. 2005 Oct;272(20):5291-305
16218959
Protein Eng Des Sel. 2004 Apr;17(4):349-56
15115854
EMBO J. 2003 May 1;22(9):2025-35
12727870
Proteomics. 2006 Apr;6 Suppl 1:S237-44
16534749
Cell. 2001 Dec 28;107(7):881-91
11779464
J Cell Biol. 2007 Jul 2;178(1):15-22
17591919
FEBS Lett. 2007 Jul 31;581(19):3641-51
17481612
Mol Biol Cell. 2006 Jun;17(6):2604-16
16571669
J Biol Chem. 2008 Jul 18;283(29):20495-504
18424781
Am J Pathol. 2007 Nov;171(5):1419-30
17916599
J Biol Chem. 1995 Jun 2;270(22):13254-61
7768924
J Biol Chem. 1999 Apr 30;274(18):12642-9
10212244
Nature. 2005 Oct 20;437(7062):1173-8
16189514
Biochem J. 2000 Aug 15;350 Pt 1:1-18
10926821
Biol Cell. 2003 May-Jun;95(3-4):169-78
12867081
J Biol Chem. 2000 Dec 22;275(51):40392-9
11007769
J Biol Chem. 2007 Jun 15;282(24):17758-66
17442665
J Cell Sci. 2005 Jul 1;118(Pt 13):2791-801
15976441
N Engl J Med. 2003 Jun 19;348(25):2543-56
12815141
Cancer Cell. 2007 Jun;11(6):498-512
17560332
J Biol Chem. 1999 Apr 16;274(16):11267-74
10196215
J Biol Chem. 1989 Mar 25;264(9):5031-5
2538469
Nature. 2003 Dec 18;426(6968):803-9
14685229
J Biol Chem. 2003 Jun 20;278(25):22183-6
12724317
J Biol Chem. 2006 Oct 6;281(40):30223-33
16891305