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| | Figure1: Perlecan as a Scaffold: Functional Uncoupling by Proteolysis (from Farach-Carson and Carson, 2007). |
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| Description | 4,391 amino acids; 468,825 (core protein) to ~850,000 Da (depends upon amount of glycosaminoglycan (GAG) additions). Perlecan is composed of 5 domains. Following a 21 amino acid signal peptide for ER targeting is the N-terminal domain I, spanning amino acids 22-193 (Murdoch et al., 1992). Domain I contains 3 SGD sequences for attachment of heparan sulfate (HS) and/or chondroitin sulfate (CS) GAGs on serine residues, and a 120 amino acid SEA (Sperm protein, Enterokinase, Agrin) module. The SEA module has no definitive function, but deletion studies in domain I suggest it increases HS chain attachment (Dolan et al., 1997). Domain I of this protein is unique to perlecan, as it shares no significant homology with any other protein (Murdoch et al., 1992). The 210 amino acid domain II (amino acids 194-403) contains 4 cysteine-rich low-density lipoprotein (LDL) receptor-like modules. Adjacent to this is one immunoglobulin G (IgG)-like repeat (residues 404-504). Domain III (1,172 amino acids; residues 505-1676) consists of modules homologous to the short arm laminin alpha-chains including 3 laminin domain IV-like modules and eight laminin epidermal growth factor (EGF)-like repeats. Domain IV is the largest domain (2010 amino acids; residues 1677-3686), containing 21 IgG-like repeats (murine perlecan has only 14 IgG-like repeats, missing IgG repeats 5-12) similar to neural cell adhesion molecules (N-CAM). Domain V (705 amino acids; residues 3687-4391) has 3 modules with sequence homology to the globular domain of laminin alpha-chains and agrin. In addition, this domain contains 4 interspersed EGF-like repeats, and another GAG chain attachment site. Domain V of perlecan also is referred to as endorepellin for its angiostatic properties and was shown to be cleaved from perlecan by BMP-1/mTLL (Mongiat et al., 2003; Gonzalez et al., 2005). Several other cleavage sites are predicted for perlecan including sites for thrombin, plasmin, collagenase, and stromelysin, although some sites may be cryptic (Whitelock et al., 1996; d'Ortho et al., 1997). |
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| | Figure 2: from Farach-Carson and Carson, 2007. |
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| Expression | Perlecan is expressed in the basement membranes of pituitary gland, skin, breast, thymus, prostate, colon, liver, pancreas, spleen, heart, and lung. Vascular basement membranes also express perlecan. In the subendothelial region, perlecan is highly expressed in the liver's perisinusoidal space, spleen, lymph nodes, and pituitary gland (Murdoch et al., 1994). In the kidney, perlecan is found in the mesangium, Bowman's capsule, the tubular basement membrane, but is only slightly expressed in the glomerular basement membrane (Groffen et al., 1997). In bone, marrow but not the mineral compartment, is rich in perlecan (Schofield et al., 1999). In human fetal tissue (12-14 week old), pericellular perlecan expression was detected in the rudiment and growth plate chondrocytes, and was found in the perichondrial capillary networks and cartilage canals (Melrose et al., 2004). |
| Localisation | Perlecan is found in the extracellular matrix (ECM), most commonly in the basement membrane underlying epithelial and endothelial cells. It also is found at high levels in cartilage, bone marrow and in muscle tissue. |
| Function | Perlecan is a multifunctional protein involved in maintaining the basement membrane, growth factor binding and signaling, cell differentiation, angiogenesis, neuromuscular function and bone development. Perlecan is an important component of the basement membrane. It binds several other basement membrane proteins including aminin 1, fibronectin, nidogen, PRELP, and collagen IV via its core protein or HS chains (Sasaki et al., 1998; Hopf et al., 2001; Kvansakul et al., 2001; Bengtsson et al., 2002). Endorepellin (domain V) also interacts with cell surface integrins (alpha2beta1), forming additional complexes linking the ECM with the cell (Bix et al., 2004). The loss of perlecan and the basement membrane architecture is sometimes indicative of carcinomas, as is the case with invasive breast carcinoma (Nerlich et al., 1997). Perlecan has extensive growth factor regulating functions afforded to its ability to bind, sequester, and activate growth factors and growth factor binding proteins. This function connects perlecan to several actions concerning cell differentiation and proliferation. Perlecan has both pro-angiogenic (whole molecule) and anti-angiogenic (endorepellin) properties, linked to its ability regulate factors such as VEGF and FGF2. Consequently, perlecan has been implicated in supporting tumor angiogenesis in several cancers (reviewed in Bix and Iozzo, 2008). In all, perlecan has been shown to bind many growth factors including BMP-2, CTGF, PDGF, several FGFs, and VEGF and modulate several others (reviewed in Bix and Iozzo, 2008; Melrose et al., 2008). Perlecan has important functions in bone development. Perlecan sustains growth plate chondrocyte organization and hypertrophic chondrocytes, greatly assists endochondral ossification, and maintains cartilage stability in general (Arikawa-Hirasawa et al., 1999; Costell et al., 1999). The complex structure and function of perlecan suggest that it acts as an extracellular matrix scaffold. Based upon rotary shadowing of individual domains and atomic force microscopy, intact perlecan is predicted to span 100-200 nm (Chakravarti et al., 1995; Costell et al., 1996; Brown et al., 1997; Dolan et al., 1997; Hopf et al., 1999; Chen and Hansma, 2000). Given that this matches the dimensions of other scaffolding domains and that perlecan has a modular structure capable of binding many partners at once, perlecan may create stable "signalosomes" by clustering transmembrane proteins and stabilizing their interactions. As a result, perlecan may be essential in directing cell signaling and hence function as an extracellular signaling scaffold (Farach-Carson and Carson, 2007). |
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| | Figure 3: Perlecan as a Scaffold: Domains and interactions (from Farach-Carson and Carson, 2007). |
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| Homology | Mouse (~85%), Chicken (67%), Zebrafish (62%), Fruitfly (35%), Worm (35%). |
| Entity | Prostate Cancer |
| Note | Perlecan expression was correlated with aggressive prostate tumors (high Gleason score). Primary prostate cancer tumors and metastatic prostate cancer to the lung and liver showed increased perlecan expression, but metastasis to the lymph nodes showed decreased perlecan protein expression. Furthermore, perlecan expression was shown to promote survival of tumors in low androgen and/or low growth factor environments. Perlecan may mediate prostate cancer progression through its regulation of the sonic hedgehog signaling pathway, whose activity has been implicated in prostate cancer (Datta et al., 2006). Targeted reduction of perlecan in prostate cancer xenografts growing in mice reduced tumor growth and vascularization (Savorè et al., 2005). |
| Disease | Prostate cancer is an adenocarcimona affecting the gland cells of the prostate. It is a slow growing cancer usually affecting older men. The most common site of metastasis of prostate cancer is the bone. |
| | |
| Entity | Breast Cancer |
| Note | Perlecan mRNA expression was shown to be increased in invasive breast carcinomas, yet immunohistochemical analysis showed a lack of perlecan deposition in the carcinoma (Nerlich et al., 1997; Nerlich et al., 1998). This suggests subsequent proteolytic cleavage of perlecan or translational defects in breast cancer. However, in breast cancer stromal cells, high perlecan deposition was also reported (Iozzo et al., 1994). |
| Disease | Breast cancer refers to the many types of cancer affecting breast tissue including ductal carcinoma and lobular carcinoma. Breast cancers are further defined as in situ or invasive. An especially deadly form is inflammatory breast cancer. The most common target of breast cancer metastasis is the lymphatic system. It is the most common form of cancer for women and the second cause of cancer-related deaths for women. |
| Prognosis | None |
| | |
| Entity | Melanoma |
| Note | In metastatic melanoma, perlecan mRNA expression was increased 15 fold over normal tissue, which correlated with enhanced perlecan deposition in the melanoma's pericellular matrix (Cohen et al., 1994). When perlecan expression was blocked with a perlecan antisense cDNA construct in metastatic melanoma cells, the proliferative and invasive properties were reduced. Perlecan serves as a reservoir for growth factors involved in angiogenesis and proliferation (VEGF, bFGF/FGF-2, FGF-7), and is needed for growth factor signaling. bFGF/FGF-2 was shown to be an important autocrine regulator of metastatic melanoma, and perlecan is needed for bFGF to advance melanoma. Without perlecan, growth factor activity is diminished, abrogating tumor progression (Adatia et al., 1997). |
| Disease | Melanoma is a type of skin cancer originating in the melanocytes. |
| Prognosis | None |
| | |
| Entity | Colon cancer |
| Note | When perlecan was blocked by antisense targeting in xenografts with human colon carcinoma cells and tumor allografts, tumor progression and neovascularization were substantially decreased in a mouse model. Perlecan inhibition is thought to suppress FGF-7 binding and receptor activation, thereby blocking tumor growth and angiogenesis (Sharma et al., 1998). As in other cancers, perlecan is a contributing factor in colon cancer progression. |
| Disease | Colon cancer usually begins as a non-cancerous adenomatous polyp and spreads into the wall of the colon, where it may metastasize through blood vessels or the lymphatic system. |
| Prognosis | None |
| | |
| Entity | Fibrosarcoma |
| Note | In contrast to other cancers, when perlecan was suppressed by antisense cDNA in fibrosarcoma cells, the phenotype became more aggressive in that they had increased migration, invasion, and adhesiveness to type IV collagen substrates. Perlecan action in fibrosarcoma is thought to be independent of the bFGF pathway and possibly prevent mesenchymal tumor invasion (Mathiak et al., 1997). |
| Disease | Fibrosarcoma is a type of malignant tumor originating in the connective tissue, mostly affecting the leg, arm, and jawbone in humans. |
| Prognosis | None |
| | |
| Entity | Adenoid cystic carcinoma (ACC) |
| Note | Perlecan expression was increased in ACC cells forming small stromal pseudocysts, but not in advanced flat ACC cells producing large pseudocysts or already attached to peripheral nerves, which have abundant perlecan. This suggests perlecan is needed for initial ACC cell growth (Kimura et al., 2000). |
| Disease | ACC is a tumor affecting the salivary glands. It is usually slow growing and not as aggressive as other salivary gland cancers. |
| Prognosis | None |
| | |
| Entity | Intrahepatic cholangiocarcinoma (ICC) |
| Note | Perlecan is highly expressed in the tumor specific fibro-myxoid stroma of ICC. In addition, the ICC cells on the invading fronts expressed higher levels of perlecan than other ICC cells, suggesting that perlecan is an important component of ICC tumor invasiveness (Sabit et al., 2001). |
| Disease | ICC is a tumor originating in the biliary system (bile ducts) of the liver. It is associated with the hepatitis C virus and chronic cholangitis. |
| Prognosis | None |
| | |
| Entity | Amyloidosis and related diseases |
| Note | In a murine model of AA amyloidogenesis perlecan expression increased before the deposits of AA amyloids, indicating that perlecan is required for the earliest stages of amyloid fibrillogenesis (Ailles et al., 1993). Perlecan was shown to accelerate beta-amyloid fibril formation and also stabilize the formed fibrils, demonstrating perlecan's role in beta-amyloidogenesis in Alzheimer's disease (Castillo et al., 1997). In addition, during hemodialysis induced beta2-microglobulin (beta2M) amyloidosis, increased amounts of HSPGs, like perlecan, direct where beta2M deposits will occur and assist fibrillogenesis (Ohashi, 2001). |
| Disease | Amyloidosis refers to a wide spectrum of diseases where the abnormal deposition of amyloid species (insoluble proteins in a beta-pleated secondary conformation) occurs in any organ or tissue. Alzheimer's disease is an example of amyloidosis affecting the brain. |
| Prognosis | None |
| | |
| Entity | Schwartz-Jampel Syndrome (SJS) |
| Note | Mutations in the perlecan gene were implicated in SJS in 2000 by (Nicole et al., 2000). Two mutations are found in the C-terminal region of domain III, SJS1-H C1532Y and SJS1-B 4740G→A, resulting in lost disulfide bonds. One mutation was found in domain IV, SJS1-A IVS64+4a→g, leaving a truncated protein missing domain IV Ig-like repeats 13-21 and domain V. (Arikawa-Hirasawa et al., 2002) reported additional mutations resulting in early stop codons. (Stum et al., 2006) reported an additional 22 perlecan mutations. In all of these mutational analyses, no evidence of a founder effect existed. The mutated perlecan proteins are secreted in lower amounts or are more susceptible to proteases and have varying degrees of functionality, resulting in the defects characteristic of SJS. However, (Rodgers et al., 2007) using mice with site specific perlecan mutations suggested that it was not the truncated protein or faulty secretion, but a downregulation of perlecan at the transcriptional level. With respect to myotonia, perlecan was shown to localize acetylcholinesterase (AChE) to the neuromuscular junction. With less functional perlecan, AChE is largely absent at the synapse, resulting in a higher concentration of ACh. This aberrantly stimulates the ACh receptor causing muscle contractions associated with myotonia. |
| Disease | SJS is a rare autosomal recessive disease characterized by skeletal dysplasias and myotonia, a neuromuscular disorder resulting in prolonged muscle contraction. Patients with the disorder have short stature, blepharophimosis (drooping eyelids with reduced size, flat nasal bridge, underdeveloped orbital rim), pursed lips, low-set ears, myopia, and a fixed facial expression. SJS is characterized by several skeletal dysplasias including kyphoscloliosis, platyspondyly (flattened vertebrae), joint contractures, and metaphyseal and epiphyseal dysplasias. Based upon clinical examination, several other disorders including kyphomelic chondrodyplasia, Burton's disease, micromelic chondrodysplasia were suggested by (Spranger et al., 2000) to be reclassified as SJS. |
| | |
| Entity | Dyssegmental dysplasia, Silverman-Handmaker type (DDHS) |
| Note | Functional null mutations of perlecan have been implicated in DDHS. (Arikawa-Hirasawa et al., 2001) reported an 89-bp duplication in exon 34, and a 5' donor site mutation in intron 52 and exon 73, resulting in a truncated perlecan protein core. In contrast to SJS, the truncated perlecan protein is not secreted and deposited, causing a functional null mutation similar to the homozygous perlecan knockout mice. This manifests in more severe defects than SJS, as all DDHS individuals are stillbirths or die shortly thereafter. |
| Disease | DDSH is a rare autosomal recessive lethal disease characterized by severe skeletal dysplasias, anisospondyly and micromelia. DDSH patients also have a flat face, cleft palate, low joint mobility, micrognathia (undersized jaw), and encephalocoele. The endochondral growth plate has shortening defects, the resting cartilage shows mucoid degeneration, and hypertrophic chondrocytes produce calcospherites that fail to fuse. |
| | |
| Entity | Intracranial aneurysms |
| Note | Two SNPs in the perlecan gene were associated with intracranial aneurysms (Ruigrok et al., 2006). A defect in perlecan is thought to contribute to faulty ECM in the arterial wall, increasing the likelihood of an aneurysm. |
| Disease | An aneurysm is the dilation of the arterial wall due to defects in the ECM. A dilated blood vessel may rupture resulting in a subarachnoid hemorrhage. |
| | |
| Primary structure of the human heparan sulfate proteoglycan from basement membrane (HSPG2/perlecan). A chimeric molecule with multiple domains homologous to the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor. |
| Murdoch AD, Dodge GR, Cohen I, Tuan RS, Iozzo RV. |
| J Biol Chem. 1992 Apr 25;267(12):8544-57. |
| PMID 1569102 |
| |
| Induction of perlecan gene expression precedes amyloid formation during experimental murine AA amyloidogenesis. |
| Ailles L, Kisilevsky R, Young ID. |
| Lab Invest. 1993 Oct;69(4):443-8. |
| PMID 8231112 |
| |
| Structural characterization of the complete human perlecan gene and its promoter. |
| Cohen IR, Grassel S, Murdoch AD, Iozzo RV. |
| Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10404-8. |
| PMID 8234307 |
| |
| Abnormal expression of perlecan proteoglycan in metastatic melanomas. |
| Cohen IR, Murdoch AD, Naso MF, Marchetti D, Berd D, Iozzo RV. |
| Cancer Res. 1994 Nov 15;54(22):5771-4. |
| PMID 7954396 |
| |
| The biology of perlecan: the multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices. |
| Iozzo RV, Cohen IR, Grassel S, Murdoch AD. |
| Biochem J. 1994 Sep 15;302 ( Pt 3):625-39. (REVIEW) |
| PMID 7945186 |
| |
| Widespread expression of perlecan proteoglycan in basement membranes and extracellular matrices of human tissues as detected by a novel monoclonal antibody against domain III and by in situ hybridization. |
| Murdoch AD, Liu B, Schwarting R, Tuan RS, Iozzo RV. |
| J Histochem Cytochem. 1994 Feb;42(2):239-49. |
| PMID 7507142 |
| |
| Recombinant domain III of perlecan promotes cell attachment through its RGDS sequence. |
| Chakravarti S, Horchar T, Jefferson B, Laurie GW, Hassell JR. |
| J Biol Chem. 1995 Jan 6;270(1):404-9. |
| PMID 7814401 |
| |
| Structural characterization of recombinant domain II of the basement membrane proteoglycan perlecan. |
| Costell M, Sasaki T, Mann K, Yamada Y, Timpl R. |
| FEBS Lett. 1996 Nov 4;396(2-3):127-31. |
| PMID 8914972 |
| |
| The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin, and heparanases. |
| Whitelock JM, Murdoch AD, Iozzo RV, Underwood PA. |
| J Biol Chem. 1996 Apr 26;271(17):10079-86. |
| PMID 8626565 |
| |
| Suppression of invasive behavior of melanoma cells by stable expression of anti-sense perlecan cDNA. |
| Adatia R, Albini A, Carlone S, Giunciuglio D, Benelli R, Santi L, Noonan DM. |
| Ann Oncol. 1997 Dec;8(12):1257-61. |
| PMID 9496392 |
| |
| The C-terminal domain V of perlecan promotes beta1 integrin-mediated cell adhesion, binds heparin, nidogen and fibulin-2 and can be modified by glycosaminoglycans. |
| Brown JC, Sasaki T, Gohring W, Yamada Y, Timpl R. |
| Eur J Biochem. 1997 Nov 15;250(1):39-46. |
| PMID 9431988 |
| |
| Perlecan binds to the beta-amyloid proteins (A beta) of Alzheimer's disease, accelerates A beta fibril formation, and maintains A beta fibril stability. |
| Castillo GM, Ngo C, Cummings J, Wight TN, Snow AD. |
| J Neurochem. 1997 Dec;69(6):2452-65. |
| PMID 9375678 |
| |
| Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. |
| d'Ortho MP, Will H, Atkinson S, Butler G, Messent A, Gavrilovic J, Smith B, Timpl R, Zardi L, Murphy G. |
| Eur J Biochem. 1997 Dec 15;250(3):751-7. |
| PMID 9461298 |
| |
| Identification of sites in domain I of perlecan that regulate heparan sulfate synthesis. |
| Dolan M, Horchar T, Rigatti B, Hassell JR. |
| J Biol Chem. 1997 Feb 14;272(7):4316-22. |
| PMID 9020150 |
| |
| Evidence for the existence of multiple heparan sulfate proteoglycans in the human glomerular basement membrane and mesangial matrix. |
| Groffen AJ, Hop FW, Tryggvason K, Dijkman H, Assmann KJ, Veerkamp JH, Monnens LA, Van den Heuvel LP. |
| Eur J Biochem. 1997 Jul 1;247(1):175-82. |
| PMID 9249024 |
| |
| Structural and functional characterization of the human perlecan gene promoter. Transcriptional activation by transforming growth factor-beta via a nuclear factor 1-binding element. |
| Iozzo RV, Pillarisetti J, Sharma B, Murdoch AD, Danielson KG, Uitto J, Mauviel A. |
| J Biol Chem. 1997 Feb 21;272(8):5219-28. |
| PMID 9030592 |
| |
| A role for perlecan in the suppression of growth and invasion in fibrosarcoma cells. |
| Mathiak M, Yenisey C, Grant DS, Sharma B, Iozzo RV. |
| Cancer Res. 1997 Jun 1;57(11):2130-6. |
| PMID 9187109 |
| |
| Gene expression and protein deposition of major basement membrane components and TGF-beta 1 in human breast cancer. |
| Nerlich AG, Wiest I, Wagner E, Sauer U, Schleicher ED. |
| Anticancer Res. 1997 Nov-Dec;17(6D):4443-9. |
| PMID 9494547 |
| |
| Morphological aspects of altered basement membrane metabolism in invasive carcinomas of the breast and the larynx. |
| Nerlich AG, Lebeau A, Hagedorn HG, Sauer U, Schleicher ED. |
| Anticancer Res. 1998 Sep-Oct;18(5A):3515-20. |
| PMID 9858933 |
| |
| Inhibition of glycosaminoglycan modification of perlecan domain I by site-directed mutagenesis changes protease sensitivity and laminin-1 binding activity. |
| Sasaki T, Costell M, Mann K, Timpl R. |
| FEBS Lett. 1998 Sep 18;435(2-3):169-72. |
| PMID 9762901 |
| |
| Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo. |
| Sharma B, Handler M, Eichstetter I, Whitelock JM, Nugent MA, Iozzo RV. |
| J Clin Invest. 1998 Oct 15;102(8):1599-608. |
| PMID 9788974 |
| |
| Transcriptional silencing of perlecan gene expression by interferon-gamma. |
| Sharma B, Iozzo RV. |
| J Biol Chem. 1998 Feb 20;273(8):4642-6. |
| PMID 9468523 |
| |
| Perlecan is essential for cartilage and cephalic development. |
| Arikawa-Hirasawa E, Watanabe H, Takami H, Hassell JR, Yamada Y. |
| Nat Genet. 1999 Nov;23(3):354-8. |
| PMID 10545953 |
| |
| Perlecan maintains the integrity of cartilage and some basement membranes. |
| Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fassler R. |
| J Cell Biol. 1999 Nov 29;147(5):1109-22. |
| PMID 10579729 |
| |
| Recombinant domain IV of perlecan binds to nidogens, laminin-nidogen complex, fibronectin, fibulin-2 and heparin. |
| Hopf M, Gohring W, Kohfeldt E, Yamada Y, Timpl R. |
| Eur J Biochem. 1999 Feb;259(3):917-25. |
| PMID 10092882 |
| |
| Expression of proteoglycan core proteins in human bone marrow stroma. |
| Schofield KP, Gallagher JT, David G. |
| Biochem J. 1999 Nov 1;343 Pt 3:663-8. |
| PMID 10527946 |
| |
| Basement membrane macromolecules: insights from atomic force microscopy. |
| Chen CH, Hansma HG. |
| J Struct Biol. 2000 Jul;131(1):44-55. |
| PMID 10945969 |
| |
| Perlecan (heparan sulfate proteoglycan) gene expression reflected in the characteristic histological architecture of salivary adenoid cystic carcinoma. |
| Kimura S, Cheng J, Ida H, Hao N, Fujimori Y, Saku T. |
| Virchows Arch. 2000 Aug;437(2):122-8. |
| PMID 10993271 |
| |
| Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia). |
| Nicole S, Davoine CS, Topaloglu H, Cattolico L, Barral D, Beighton P, Hamida CB, Hammouda H, Cruaud C, White PS, Samson D, Urtizberea JA, Lehmann-Horn F, Weissenbach J, Hentati F, Fontaine B. |
| Nat Genet. 2000 Dec;26(4):480-3. |
| PMID 11101850 |
| |
| Spectrum of Schwartz-Jampel syndrome includes micromelic chondrodysplasia, kyphomelic dysplasia, and Burton disease. |
| Spranger J, Hall BD, Hane B, Srivastava A, Stevenson RE. |
| Am J Med Genet. 2000 Oct 2;94(4):287-95. |
| PMID 11038441 |
| |
| Dyssegmental dysplasia, Silverman-Handmaker type: unexpected role of perlecan in cartilage development. |
| Arikawa-Hirasawa E, Wilcox WR, Yamada Y. |
| Am J Med Genet. 2001 Winter;106(4):254-7. (REVIEW) |
| PMID 11891676 |
| |
| Mapping of binding sites for nidogens, fibulin-2, fibronectin and heparin to different IG modules of perlecan. |
| Hopf M, Gohring W, Mann K, Timpl R. |
| J Mol Biol. 2001 Aug 17;311(3):529-41. |
| PMID 11493006 |
| |
| Structural basis for the high-affinity interaction of nidogen-1 with immunoglobulin-like domain 3 of perlecan. |
| Kvansakul M, Hopf M, Ries A, Timpl R, Hohenester E. |
| Embo J. 2001 Oct 1;20(19):5342-6. |
| PMID 11574465 |
| |
| Pathogenesis of beta2-microglobulin amyloidosis. |
| Ohashi K. |
| Pathol Int. 2001 Jan;51(1):1-10. (REVIEW) |
| PMID 11148456 |
| |
| Enhanced expression of basement-membrane-type heparan sulfate proteoglycan in tumor fibro-myxoid stroma of intrahepatic cholangiocarcinoma. |
| Sabit H, Tsuneyama K, Shimonishi T, Harada K, Cheng J, Ida H, Saku T, Saito K, Nakanuma Y. |
| Pathol Int. 2001 Apr;51(4):248-56. |
| PMID 11350606 |
| |
| Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia. |
| Arikawa-Hirasawa E, Le AH, Nishino I, Nonaka I, Ho NC, Francomano CA, Govindraj P, Hassell JR, Devaney JM, Spranger J, Stevenson RE, Iannaccone S, Dalakas MC, Yamada Y. |
| Am J Hum Genet. 2002 May;70(5):1368-75. |
| PMID 11941538 |
| |
| The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement membrane anchor. |
| Bengtsson E, Morgelin M, Sasaki T, Timpl R, Heinegard D, Aspberg A. |
| J Biol Chem. 2002 Apr 26;277(17):15061-8. |
| PMID 11847210 |
| |
| MEC-8 regulates alternative splicing of unc-52 transcripts in C. elegans hypodermal cells. |
| Spike CA, Davies AG, Shaw JE, Herman RK. |
| Development. 2002 Nov;129(21):4999-5008. |
| PMID 12397108 |
| |
| Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan. |
| Mongiat M, Sweeney SM, San Antonio JD, Fu J, Iozzo RV. |
| J Biol Chem. 2003 Feb 7;278(6):4238-49. |
| PMID 12435733 |
| |
| Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha2beta1 integrin. |
| Bix G, Fu J, Gonzalez EM, Macro L, Barker A, Campbell S, Zutter MM, Santoro SA, Kim JK, Hook M, Reed CC, Iozzo RV. |
| J Cell Biol. 2004 Jul 5;166(1):97-109. |
| PMID 15240572 |
| |
| Perlecan immunolocalizes to perichondrial vessels and canals in human fetal cartilaginous primordia in early vascular and matrix remodeling events associated with diarthrodial joint development. |
| Melrose J, Smith S, Whitelock J. |
| J Histochem Cytochem. 2004 Nov;52(11):1405-13. |
| PMID 15505335 |
| |
| BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan. |
| Gonzalez EM, Reed CC, Bix G, Fu J, Zhang Y, Gopalakrishnan B, Greenspan DS, Iozzo RV. |
| J Biol Chem. 2005 Feb 25;280(8):7080-7. |
| PMID 15591058 |
| |
| Perlecan knockdown in metastatic prostate cancer cells reduces heparin-binding growth factor responses in vitro and tumor growth in vivo. |
| Savore C, Zhang C, Muir C, Liu R, Wyrwa J, Shu J, Zhau HE, Chung LW, Carson DD, Farach-Carson MC. |
| Clin Exp Metastasis. 2005;22(5):377-90. |
| PMID 16283481 |
| |
| Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway. |
| Datta MW, Hernandez AM, Schlicht MJ, Kahler AJ, DeGueme AM, Dhir R, Shah RB, Farach-Carson C, Barrett A, Datta S. |
| Mol Cancer. 2006 5:9. |
| PMID 16507112 |
| |
| Evidence in favor of the contribution of genes involved in the maintenance of the extracellular matrix of the arterial wall to the development of intracranial aneurysms. |
| Ruigrok YM, Rinkel GJ, van't Slot R, Wolfs M, Tang S, Wijmenga C. |
| Hum Mol Genet. 2006 Nov 15;15(22):3361-8. |
| PMID 17038484 |
| |
| Spectrum of HSPG2 (Perlecan) mutations in patients with Schwartz-Jampel syndrome. |
| Stum M, Davoine CS, Vicart S, Guillot-Noel L, Topaloglu H, Carod-Artal FJ, Kayserili H, Hentati F, Merlini L, Urtizberea JA, Hammouda el-H, Quan PC, Fontaine B, Nicole S. |
| Hum Mutat. 2006 Nov;27(11):1082-91. |
| PMID 16927315 |
| |
| Perlecan--a multifunctional extracellular proteoglycan scaffold. |
| Farach-Carson MC, Carson DD. |
| Glycobiology. 2007 Sep;17(9):897-905. (REVIEW) |
| PMID 17442708 |
| |
| Reduced perlecan in mice results in chondrodysplasia resembling Schwartz-Jampel syndrome. |
| Rodgers KD, Sasaki T, Aszodi A, Jacenko O. |
| Hum Mol Genet. 2007 Mar 1;16(5):515-28. |
| PMID 17213231 |
| |
| Novel interactions of perlecan: unraveling perlecan's role in angiogenesis. |
| Bix G, Iozzo RV. |
| Microsc Res Tech. 2008 May;71(5):339-48. (REVIEW) |
| PMID 18300285 |
| |
| Perlecan, the "jack of all trades" proteoglycan of cartilaginous weight-bearing connective tissues. |
| Melrose J, Hayes AJ, Whitelock JM, Little CB. |
| Bioessays. 2008 May;30(5):457-69. (REVIEW) |
| PMID 18404701 |
| |
