Membrane-anchored serine proteases in health and disease.
Serine proteases of the trypsin-like family have long been recognized to be critical effectors of biological processes as diverse as digestion, blood coagulation, fibrinolysis, and immunity. In recent years, a subgroup of these enzymes has been identified that are anchored directly to plasma membranes, either by a carboxy-terminal transmembrane domain (Type I), an amino-terminal transmembrane domain with a cytoplasmic extension (Type II or TTSP), or through a glycosylphosphatidylinositol (GPI) linkage. Recent biochemical, cellular, and in vivo analyses have now established that membrane-anchored serine proteases are key pericellular contributors to processes vital for development and the maintenance of homeostasis. This chapter reviews our current knowledge of the biological and physiological functions of these proteases, their molecular substrates, and their contributions to disease.
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Toni M
TM
Antalis
Thomas H
TH
Bugge
Qingyu
Q
Wu
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D004194:Disease; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006262:Health; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology; D057057:Serine Proteases / Q000737:chemistry / Q000378:metabolism*
D017261:Glycosylphosphatidylinositols; D011480:Protease Inhibitors; D057057:Serine Proteases
Circ Heart Fail. 2010 Mar;3(2):207-11
20061521
Cancer Res. 2009 Nov 1;69(21):8395-402
19843851
Cancer Res. 2003 Mar 1;63(5):1101-5
12615728
Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):419-21
10224463
J Biol Chem. 2008 Apr 18;283(16):10535-42
18263585
Genomics. 1997 Sep 15;44(3):309-20
9325052
Dev Cell. 2010 Jan 19;18(1):25-38
20152175
J Biol Chem. 2002 Mar 22;277(12):10539-46
11792696
J Biol Chem. 2002 May 10;277(19):16976-84
11861648
Nat Genet. 2001 Jan;27(1):59-63
11137999
Front Biosci. 2008 Jan 01;13:1991-2000
17981686
J Biol Chem. 2002 Oct 11;277(41):38390-8
12154094
Biol Reprod. 2009 Nov;81(5):921-32
19571264
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8525-9
10880574
FEBS Lett. 2000 Jan 28;466(2-3):295-9
10682847
J Soc Gynecol Investig. 2000 Nov-Dec;7(6):358-62
11111072
Cancer Res. 1995 May 1;55(9):1856-62
7728753
J Biol Chem. 2003 Jul 11;278(28):25847-52
12736257
J Biol Chem. 2000 Aug 25;275(34):26333-42
10831593
Cancer Res. 1999 Sep 1;59(17):4180-4
10485450
Immunogenetics. 1999 May;49(5):420-8
10199918
Biochem J. 2003 Aug 1;373(Pt 3):689-702
12744720
Circulation. 2005 Oct 18;112(16):2403-10
16216958
Clin Cancer Res. 2002 Apr;8(4):1101-7
11948120
Histochemistry. 1983;78(2):251-70
6409850
Am J Pathol. 2006 May;168(5):1513-25
16651618
Biochem J. 2006 Dec 15;400(3):551-61
16872279
Chest. 2007 Nov;132(5):1631-6
17998363
Clin Genet. 2008 Jul;74(1):47-53
18445049
J Cancer Res Clin Oncol. 2006 Dec;132(12):765-70
16810501
Am J Physiol Cell Physiol. 2006 Dec;291(6):C1258-70
16822939
J Biochem. 2001 Sep;130(3):425-30
11530019
J Cell Biochem. 2005 Jun 1;95(3):632-47
15832373
Eur J Biochem. 1997 Oct 15;249(2):612-21
9370374
Front Biosci (Elite Ed). 2009 Jun 01;1:242-9
19482641
JOP. 2009 Sep 04;10(5):501-6
19734625
J Biol Chem. 2000 Nov 24;275(47):36720-5
10962009
J Biol Chem. 1998 May 8;273(19):11895-901
9565616
J Biol Chem. 1993 Nov 5;268(31):23311-7
8226855
Am J Physiol Lung Cell Mol Physiol. 2007 May;292(5):L1263-72
17237151
Biochem Biophys Res Commun. 2004 Nov 12;324(2):953-63
15474520
Am J Pathol. 2008 Nov;173(5):1464-75
18832587
J Biol Chem. 2007 Mar 2;282(9):6153-60
17199078
J Biol Chem. 2008 Dec 12;283(50):34864-72
18922802
Int J Biochem Cell Biol. 2008;40(6-7):1297-316
18191610
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4937-41
7685111
Front Biosci. 2008 Jan 01;13:621-35
17981575
Arch Dis Child. 1975 Apr;50(4):277-82
1147667
J Biol Chem. 1999 May 21;274(21):14926-35
10329693
Nat Genet. 2008 May;40(5):569-71
18408718
Front Biosci. 2008 Jan 01;13:754-8
17981585
Biochim Biophys Acta. 2000 Jun 21;1492(1):63-71
11004480
Hypertension. 2005 Oct;46(4):683-8
16172430
Structure. 2003 Sep;11(9):1123-31
12962630
Proc Soc Exp Biol Med. 1994 Jun;206(2):114-8
8208733
Kidney Int. 2009 Jan;75(2):142-6
18716601
FEBS Lett. 2005 Mar 28;579(9):1945-50
15792801
Protein Sci. 2009 May;18(5):1081-94
19388054
Oncogene. 2007 Mar 8;26(11):1546-56
16983341
Front Biosci. 2007 May 01;12:4179-90
17485366
Hum Mol Genet. 2002 Nov 1;11(23):2829-36
12393794
Development. 2009 Aug;136(15):2653-63
19592578
J Biol Chem. 2009 May 8;284(19):12829-36
19286660
Biochem Biophys Res Commun. 1998 Nov 18;252(2):307-12
9826525
J Virol. 2010 Jun;84(11):5605-14
20237084
J Biol Chem. 2004 Aug 13;279(33):34464-71
15192093
J Biol Chem. 2001 Jan 12;276(2):857-60
11060317
J Biol Chem. 2002 Nov 1;277(44):41906-15
12194977
Br J Cancer. 2007 Jul 16;97(2):201-9
17579619
Eur J Dermatol. 2007 Sep-Oct;17(5):375-80
17673379
Blood. 2009 May 28;113(22):5605-8
19357398
J Virol. 2006 Oct;80(19):9896-8
16973594
J Biol Chem. 2007 Sep 21;282(38):27728-35
17660514
J Biol Chem. 1997 Dec 12;272(50):31315-20
9395459
Thromb Haemost. 2003 Mar;89(3):561-72
12624642
Immunol Rev. 2007 Jun;217:141-54
17498057
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11054-61
10500122
Nat Struct Mol Biol. 2006 Jan;13(1):71-6
16369486
Hum Reprod. 2010 Mar;25(3):623-32
20089521
EMBO Mol Med. 2010 Jan;2(1):26-37
20043279
J Virol. 2009 Apr;83(7):3200-11
19158246
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7181-5
8346233
Lancet. 1971 Jan 23;1(7691):165-6
4102188
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):785-90
15637153
J Biol Chem. 1999 Jun 25;274(26):18231-6
10373424
J Biol Chem. 2001 Jun 8;276(23):20648-58
11259427
J Biol Chem. 2009 Aug 28;284(35):23177-81
19487698
Front Biosci. 2008 Jan 01;13:1557-67
17981648
Immunogenetics. 2010 Jun;62(6):369-82
20383634
Endocrinology. 2004 Apr;145(4):1898-905
14691009
Histochem Cell Biol. 2009 Dec;132(6):639-46
19847458
Histol Histopathol. 2007 Mar;22(3):305-9
17163404
Nat Rev Genet. 2003 Jul;4(7):544-58
12838346
J Pathol. 2008 Jun;215(2):118-25
18338334
Pediatr Res. 2009 Apr;65(4):443-6
19127211
Front Biosci. 2001 Feb 01;6:D192-200
11171558
J Biol Chem. 1997 Dec 12;272(50):31293-300
9395456
J Biol Chem. 1997 Apr 4;272(14):9147-52
9083044
J Gen Physiol. 1939 Mar 20;22(4):429-46
19873112
Mod Pathol. 2006 Mar;19(3):447-52
16439987
J Biol Chem. 2001 Sep 7;276(36):33293-6
11435447
Blood. 2008 Sep 15;112(6):2539-45
18523150
Bioorg Med Chem Lett. 2008 Nov 15;18(22):5895-9
18752942
Eur J Biochem. 1995 Feb 1;227(3):866-72
7867648
Am J Pathol. 2008 Dec;173(6):1693-701
18988802
Histochem Cell Biol. 2001 Mar;115(3):181-7
11326745
Circ Res. 2008 Aug 29;103(5):502-8
18669922
J Biol Chem. 1994 Jul 22;269(29):18843-8
8034638
Future Oncol. 2009 Feb;5(1):97-104
19243302
Genes Dev. 2005 Aug 15;19(16):1934-50
16103220
Clin Chem. 2010 Jul;56(7):1166-76
20489134
J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):385-90
10419016
Cancer. 2003 Nov 1;98(9):1898-904
14584072
J Biol Chem. 2003 Jul 18;278(29):26773-9
12738778
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7583-8
16672368
Cancer Res. 2001 Aug 15;61(16):5974-8
11507037
Biochem J. 2010 Aug 15;430(1):87-95
20518742
Cell Metab. 2008 Dec;8(6):502-11
18976966
J Biol Chem. 2003 Jan 31;278(5):3363-71
12441343
J Biochem. 1998 Oct;124(4):784-9
9756624
Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L385-95
16199437
J Med Invest. 2003 Feb;50(1-2):78-86
12630572
Cancer Res. 1999 Jul 1;59(13):3199-205
10397266
Am J Hum Genet. 2007 Mar;80(3):467-77
17273967
Thromb Haemost. 2003 Aug;90(2):185-93
12888865
Cancer Res. 2001 Feb 15;61(4):1686-92
11245484
FEBS Lett. 2000 Feb 18;468(1):93-100
10683448
Cancer Res. 2009 Mar 1;69(5):1828-35
19223533
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9185-90
12886014
Nat Genet. 2010 Aug;42(8):676-83
20657595
Science. 1933 Sep 1;78(2018):189-90
17730431
Mol Cell Biol. 2005 Jul;25(13):5687-98
15964823
Carcinogenesis. 2010 Apr;31(4):597-606
20118200
Am J Hypertens. 2008 Sep;21(9):1028-33
18583984
Rev Med Virol. 2010 Sep;20(5):298-310
20629046
Biochim Biophys Acta. 2000 Nov 15;1502(3):337-50
11068177
Biochem J. 2005 Jun 15;388(Pt 3):967-72
15537383
Hypertension. 2007 Apr;49(4):857-64
17296875
BMC Cancer. 2009 Jun 25;9:201
19555470
J Biol Chem. 2003 Sep 19;278(38):36341-9
12815039
FEBS J. 2009 Apr;276(8):2213-26
19302215
Biochim Biophys Acta. 2007 Jul;1773(7):1133-40
17532063
Biochemistry. 1995 Apr 11;34(14):4562-8
7718557
Development. 2008 Jan;135(2):217-25
18057101
Curr Top Dev Biol. 2007;78:23-46
17338914
Acta Otolaryngol. 2006 Mar;126(3):237-9
16618647
Head Neck. 2006 May;28(5):432-40
16320362
J Biol Chem. 2002 Mar 1;277(9):6858-63
11878264
J Biol Chem. 1999 Jan 15;274(3):1596-605
9880538
Am J Physiol Lung Cell Mol Physiol. 2004 Nov;287(5):L928-35
15246975
J Biol Chem. 1994 Aug 5;269(31):19976-82
8051081
Cancer Cell. 2004 Aug;6(2):185-95
15324701
Gut. 1977 Apr;18(4):259-65
324873
Biochem J. 2005 Aug 15;390(Pt 1):125-36
15839837
Biochem J. 2008 May 15;412(1):81-91
18215125
Br J Cancer. 2005 Feb 28;92(4):760-9
15685234
Oncogene. 2008 Apr 17;27(18):2635-47
17968309
Methods Enzymol. 1994;244:100-14
7845200
Biochem J. 2005 Aug 15;390(Pt 1):231-42
15853774
J Invest Dermatol. 2009 Apr;129(4):862-9
18843291
J Biol Chem. 1999 Jun 25;274(26):18237-42
10373425
Cancer Res. 2006 Apr 1;66(7):3611-9
16585186
J Am Soc Nephrol. 2006 Apr;17(4):968-76
16524950
Biol Pharm Bull. 2010;33(4):561-7
20410586
J Hypertens. 2009 Jan;27(1):181-9
19145783
Front Biosci. 2007 Sep 01;12:5052-9
17569629
J Biol Chem. 1995 Jan 6;270(1):66-72
7814421
Am J Physiol Renal Physiol. 2010 Oct;299(4):F854-61
20630937
J Biol Chem. 2007 Dec 14;282(50):36714-23
17940283
Thromb Haemost. 2000 Nov;84(5):865-70
11127869
J Cell Biol. 2003 Nov 24;163(4):901-10
14638864
PLoS One. 2009 Nov 17;4(11):e7870
19924243
Ann Surg. 2005 Sep;242(3):353-61; discussion 361-3
16135921
J Biol Chem. 2008 Feb 1;283(5):2478-87
18048349
Mol Med. 2006 Jan-Mar;12(1-3):1-7
16838070
Biochem J. 2010 Jun 15;428(3):325-46
20507279
Br J Cancer. 2001 Jan;84(2):237-43
11161383
J Am Soc Nephrol. 2003 Jan;14(1):11-6
12506133
Kidney Int. 2006 Oct;70(8):1432-8
16941024
J Biol Chem. 2002 Jan 18;277(3):2160-8
11696548
J Biol Chem. 2005 Oct 14;280(41):34513-20
16103126
World J Gastroenterol. 2005 Oct 21;11(39):6202-7
16273651
Biochemistry. 1988 Feb 9;27(3):1067-74
2835076
Eur J Biochem. 2001 May;268(9):2687-99
11322890
J Biol Chem. 2006 Nov 3;281(44):32941-5
16980306
Biol Reprod. 2010 Sep;83(3):359-69
20484738
J Gen Physiol. 1939 Mar 20;22(4):447-50
19873113
Nature. 2001 Aug 23;412(6849):822-6
11518967
Br J Cancer. 2005 Jan 31;92(2):278-83
15611789
Hum Pathol. 2005 Jun;36(6):626-33
16021568
Circ Heart Fail. 2009 Nov;2(6):541-8
19919978
J Virol. 2010 May;84(10):5089-96
20219906
Biochem Biophys Res Commun. 2001 Oct 5;287(4):995-1002
11573963
J Biol Chem. 2002 Mar 8;277(10):8338-45
11756432
Cancer Res. 2000 May 15;60(10):2602-6
10825129
Cancer Metastasis Rev. 2003 Jun-Sep;22(2-3):237-58
12784999
J Surg Oncol. 2008 Dec 1;98(7):559-64
18932242
J Biol Chem. 2001 Jun 15;276(24):21434-42
11274175
Lancet. 1969 Apr 19;1(7599):812-3
4180366
Biochim Biophys Acta. 2001 Mar 19;1518(1-2):204-9
11267681
J Biol Chem. 2002 Oct 4;277(40):37637-46
12149247
Am J Hum Genet. 1996 Jun;58(6):1254-9
8651303
Nature. 2007 Aug 2;448(7153):595-9
17671502
J Med Invest. 1998 Aug;45(1-4):77-86
9864967
Biochim Biophys Acta. 1993 Jun 25;1173(3):350-2
8318546
Cancer Res. 2001 Aug 1;61(15):5692-6
11479199
J Biol Chem. 2008 Nov 7;283(45):30576-84
18784072
Neoplasia. 2008 Feb;10(2):177-88
18283340
Am J Physiol Cell Physiol. 2005 Aug;289(2):C462-70
15800053
J Invest Dermatol. 2004 Apr;122(4):937-44
15102084
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5771-6
17389401
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4200-5
20142489
Hypertens Res. 2009 Apr;32(4):276-81
19262497
BMC Cancer. 2006 Jul 04;6:176
16820046
Eur J Biochem. 2000 Dec;267(23):6931-7
11082206
J Biol Chem. 2008 Oct 24;283(43):29495-504
18713750
Biol Chem. 2007 Aug;388(8):853-8
17655505
Hum Mutat. 2008 Jan;29(1):130-41
17918732
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15119-24
11742098
J Cell Biol. 2005 Aug 1;170(3):487-96
16061697
J Biol Chem. 2003 Dec 26;278(52):52363-70
14559895
Science. 2008 May 23;320(5879):1088-92
18451267
Mol Cell Biol. 2006 Feb;26(3):965-75
16428450
J Biol Chem. 1999 Oct 22;274(43):30784-93
10521469
Physiol Rev. 1997 Oct;77(4):1033-79
9354811
N Engl J Med. 2008 Jul 10;359(2):158-65
18614783
Eur J Biochem. 1999 Jun;262(3):755-64
10411637
Blood. 2006 Oct 15;108(8):2616-23
16794252
J Biol Chem. 2010 Aug 20;285(34):26162-73
20551327
Biochem Soc Trans. 2007 Jun;35(Pt 3):583-7
17511657
Biochemistry. 1973 May 22;12(11):2025-34
4705984
J Mol Cell Cardiol. 2008 Jan;44(1):131-42
17996891
J Cell Physiol. 2007 Oct;213(1):237-45
17471493
Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L932-41
18310226
Biochem Biophys Res Commun. 1999 Dec 20;266(2):564-8
10600542
J Urol. 2001 Dec;166(6):2171-7
11696729
Science. 2005 Oct 28;310(5748):644-8
16254181
J Mol Biol. 1999 Sep 17;292(2):361-73
10493881
Genes Cells. 2008 Oct;13(10):1001-13
18754795
Protein Expr Purif. 2006 Sep;49(1):47-54
16815034
Oncogene. 2005 Aug 11;24(34):5333-43
16007225
Nature. 1997 Oct 9;389(6651):607-10
9335501
Prostate. 2009 Dec 1;69(16):1790-801
19670249
Eur J Biochem. 2001 Mar;268(5):1250-8
11231276
J Am Soc Nephrol. 2000 May;11(5):828-834
10770960
Am J Physiol Regul Integr Comp Physiol. 2009 Dec;297(6):R1733-41
19793956
Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7588-92
8052624
J Gen Physiol. 2002 Aug;120(2):191-201
12149280
Am J Pathol. 2001 Apr;158(4):1301-11
11290548
Clin Exp Metastasis. 2002;19(7):639-49
12498394
Cancer Cell. 2010 May 18;17(5):443-54
20478527
Development. 2007 Oct;134(19):3461-71
17728346
J Histochem Cytochem. 2003 Aug;51(8):1017-25
12871983
Annu Rev Biochem. 1980;49:593-626
6996568
Oncogene. 2002 May 23;21(23):3765-79
12032844
J Protein Chem. 1991 Oct;10(5):475-80
1799406
Chem Rev. 2002 Dec;102(12):4751-804
12475206
J Biol Chem. 2002 Mar 1;277(9):6806-12
11741986
Am J Physiol. 1998 Feb;274(2):G342-9
9486188
Am J Respir Cell Mol Biol. 1997 Mar;16(3):300-8
9070615
Dev Biol. 2007 Mar 1;303(1):222-30
17174946
J Pharmacol Exp Ther. 2009 May;329(2):764-74
19190233
FEBS J. 2005 Dec;272(24):6387-99
16336275
FEBS J. 2007 Apr;274(8):2148-60
17388811
J Immunol. 2000 Jun 15;164(12):6566-75
10843716
J Biol Chem. 2004 Nov 5;279(45):46981-94
15328353
Am J Pathol. 2007 Aug;171(2):608-16
17620368
Clin Chim Acta. 2009 Nov;409(1-2):85-9
19751717
J Biol Chem. 2008 Sep 12;283(37):25290-25295
18650438
Cancer Res. 1993 Mar 15;53(6):1409-15
8383010
Biochem Biophys Res Commun. 1967 Apr 20;27(2):157-62
6035483
Am J Pathol. 2009 Oct;175(4):1453-63
19717635
J Med Invest. 2003 Feb;50(1-2):95-107
12630574
Biosci Biotechnol Biochem. 2008 Mar;72(3):905-8
18323639
Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):217-27
16492908
Trends Biochem Sci. 1989 Mar;14(3):110-2
2658218
Mol Cell Biochem. 2010 Apr;337(1-2):259-66
19911255
J Gen Physiol. 2008 Nov;132(5):521-35
18852303
Nat Genet. 2010 Aug;42(8):668-75
20601956
Cancer Res. 2005 Feb 1;65(3):868-78
15705885
J Clin Invest. 1998 Jan 15;101(2):321-6
9435303
Am J Pathol. 2010 Jun;176(6):2986-96
20382709
J Am Soc Nephrol. 2001 Jun;12(6):1114-1121
11373334