Caveolin 1 Explained

Caveolin-1 is a protein that in humans is encoded by the CAV1 gene.^[1]

Function

The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 MAP kinase cascade. CAV1 and CAV2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. By using alternative initiation codons in the same reading frame, two isoforms (alpha and beta) are encoded by a single transcript from this gene.^[2]

Interactions

Caveolin 1 has been shown to interact with heterotrimeric G proteins,^[3] Src tyrosine kinases (Src, Lyn) and H-Ras,^[4] cholesterol,^[5] TGF beta receptor 1,^[6] endothelial NOS,^[7] androgen receptor,^[8] amyloid precursor protein,^[9] gap junction protein, alpha 1,^[10] nitric oxide synthase 2A,^[11] epidermal growth factor receptor,^[12] endothelin receptor type B,^[13] PDGFRB,^[14] PDGFRA,^[14] PTGS2,^[15] TRAF2,^{[16] [17]} estrogen receptor alpha,^[18] caveolin 2,^{[19] [20]} PLD2,^{[21] [22]} Bruton's tyrosine kinase,^[23] and SCP2.^[24] All these interactions are through a caveolin-scaffolding domain (CSD) within caveolin-1 molecule.^[4] Molecules that interact with caveolin-1 contain caveolin-binding motifs (CBM).^[25]

See also

• Caveolin

Further reading

• Engelman JA, Zhang X, Galbiati F, Volonte D, Sotgia F, Pestell RG, Minetti C, Scherer PE, Okamoto T, Lisanti MP . Molecular genetics of the caveolin gene family: implications for human cancers, diabetes, Alzheimer disease, and muscular dystrophy . American Journal of Human Genetics . 63 . 6 . 1578–87 . December 1998 . 9837809 . 1377628 . 10.1086/302172 .
• Razani B, Schlegel A, Liu J, Lisanti MP . Caveolin-1, a putative tumour suppressor gene . Biochemical Society Transactions . 29 . Pt 4 . 494–9 . August 2001 . 11498016 . 10.1042/BST0290494 .
• Fujimoto T, Kogo H, Nakamura N, Ozeki S . [Microdomains and caveolin] . Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme . 47 . 4 Suppl . 326–32 . March 2002 . 11915322 .
• Shatz M, Liscovitch M . Caveolin-1 and cancer multidrug resistance: coordinate regulation of pro-survival proteins? . Leukemia Research . 28 . 9 . 907–8 . September 2004 . 15234566 . 10.1016/j.leukres.2004.03.013 .
• Frank PG, Lisanti MP . Caveolin-1 and liver regeneration: role in proliferation and lipogenesis . Cell Cycle . 6 . 2 . 115–6 . January 2007 . 17314510 . 10.4161/cc.6.2.3722 . free .

Notes and References

1. Fra AM, Mastroianni N, Mancini M, Pasqualetto E, Sitia R . Human caveolin-1 and caveolin-2 are closely linked genes colocalized with WI-5336 in a region of 7q31 frequently deleted in tumors . Genomics . 56 . 3 . 355–6 . March 1999 . 10087206 . 10.1006/geno.1998.5723 .
2. Web site: Entrez Gene: CAV1 caveolin 1, caveolae protein, 22kDa.
3. Li S, Okamoto T, Chun M, Sargiacomo M, Casanova JE, Hansen SH, Nishimoto I, Lisanti MP . Evidence for a regulated interaction between heterotrimeric G proteins and caveolin . The Journal of Biological Chemistry . 270 . 26 . 15693–701 . June 1995 . 7797570 . 10.1074/jbc.270.26.15693 . free .
4. Li S, Couet J, Lisanti MP . Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases . The Journal of Biological Chemistry . 271 . 46 . 29182–90 . November 1996 . 8910575 . 10.1074/jbc.271.46.29182 . 6687395 . free .
5. Li S, Song KS, Lisanti MP . Expression and characterization of recombinant caveolin. Purification by polyhistidine tagging and cholesterol-dependent incorporation into defined lipid membranes . The Journal of Biological Chemistry . 271 . 1 . 568–73 . January 1996 . 8550621 . 10.1074/jbc.271.1.568 . free .
6. Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP . Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor . The Journal of Biological Chemistry . 276 . 9 . 6727–38 . March 2001 . 11102446 . 10.1074/jbc.M008340200 . free .
7. García-Cardeña G, Fan R, Stern DF, Liu J, Sessa WC . Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin-1 . The Journal of Biological Chemistry . 271 . 44 . 27237–40 . November 1996 . 8910295 . 10.1074/jbc.271.44.27237 . free .
8. Lu ML, Schneider MC, Zheng Y, Zhang X, Richie JP . Caveolin-1 interacts with androgen receptor. A positive modulator of androgen receptor mediated transactivation . The Journal of Biological Chemistry . 276 . 16 . 13442–51 . April 2001 . 11278309 . 10.1074/jbc.M006598200 . free .
9. Ikezu T, Trapp BD, Song KS, Schlegel A, Lisanti MP, Okamoto T . Caveolae, plasma membrane microdomains for alpha-secretase-mediated processing of the amyloid precursor protein . The Journal of Biological Chemistry . 273 . 17 . 10485–95 . April 1998 . 9553108 . 10.1074/jbc.273.17.10485 . free .
10. Schubert AL, Schubert W, Spray DC, Lisanti MP . Connexin family members target to lipid raft domains and interact with caveolin-1 . Biochemistry . 41 . 18 . 5754–64 . May 2002 . 11980479 . 10.1021/bi0121656 .
11. Felley-Bosco E, Bender FC, Courjault-Gautier F, Bron C, Quest AF . Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells . Proceedings of the National Academy of Sciences of the United States of America . 97 . 26 . 14334–9 . December 2000 . 11114180 . 18919 . 10.1073/pnas.250406797 . 2000PNAS...9714334F . free .
12. Couet J, Sargiacomo M, Lisanti MP . Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities . The Journal of Biological Chemistry . 272 . 48 . 30429–38 . November 1997 . 9374534 . 10.1074/jbc.272.48.30429 . free.
13. Yamaguchi T, Murata Y, Fujiyoshi Y, Doi T . Regulated interaction of endothelin B receptor with caveolin-1 . European Journal of Biochemistry . 270 . 8 . 1816–27 . April 2003 . 12694195 . 10.1046/j.1432-1033.2003.03544.x . free .
14. Yamamoto M, Toya Y, Jensen RA, Ishikawa Y . Caveolin is an inhibitor of platelet-derived growth factor receptor signaling . Experimental Cell Research . 247 . 2 . 380–8 . March 1999 . 10066366 . 10.1006/excr.1998.4379 .
15. Liou JY, Deng WG, Gilroy DW, Shyue SK, Wu KK . Colocalization and interaction of cyclooxygenase-2 with caveolin-1 in human fibroblasts . The Journal of Biological Chemistry . 276 . 37 . 34975–82 . September 2001 . 11432874 . 10.1074/jbc.M105946200 . free .
16. Feng X, Gaeta ML, Madge LA, Yang JH, Bradley JR, Pober JS . Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors . The Journal of Biological Chemistry . 276 . 11 . 8341–9 . March 2001 . 11112773 . 10.1074/jbc.M007116200 . free .
17. Cao H, Courchesne WE, Mastick CC . A phosphotyrosine-dependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase . The Journal of Biological Chemistry . 277 . 11 . 8771–4 . March 2002 . 11805080 . 10.1074/jbc.C100661200 . free .
18. Schlegel A, Wang C, Pestell RG, Lisanti MP . Ligand-independent activation of oestrogen receptor alpha by caveolin-1 . The Biochemical Journal . 359 . Pt 1 . 203–10 . October 2001 . 11563984 . 1222136 . 10.1042/0264-6021:3590203 .
19. Breuza L, Corby S, Arsanto JP, Delgrossi MH, Scheiffele P, Le Bivic A . The scaffolding domain of caveolin 2 is responsible for its Golgi localization in Caco-2 cells . Journal of Cell Science . 115 . Pt 23 . 4457–67 . December 2002 . 12414992 . 10.1242/jcs.00130 . 14788127 .
20. Scherer PE, Lewis RY, Volonte D, Engelman JA, Galbiati F, Couet J, Kohtz DS, van Donselaar E, Peters P, Lisanti MP . Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo . The Journal of Biological Chemistry . 272 . 46 . 29337–46 . November 1997 . 9361015 . 10.1074/jbc.272.46.29337 . free .
21. Zheng X, Bollinger Bollag W . Aquaporin 3 colocates with phospholipase d2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation . The Journal of Investigative Dermatology . 121 . 6 . 1487–95 . December 2003 . 14675200 . 10.1111/j.1523-1747.2003.12614.x . free .
22. Czarny M, Fiucci G, Lavie Y, Banno Y, Nozawa Y, Liscovitch M . Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains . FEBS Letters . 467 . 2–3 . 326–32 . February 2000 . 10675563 . 10.1016/S0014-5793(00)01174-1 . 21891748 . free . 2000FEBSL.467..326C .
23. Vargas L, Nore BF, Berglof A, Heinonen JE, Mattsson PT, Smith CI, Mohamed AJ . Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx . The Journal of Biological Chemistry . 277 . 11 . 9351–7 . March 2002 . 11751885 . 10.1074/jbc.M108537200 . free .
24. Zhou M, Parr RD, Petrescu AD, Payne HR, Atshaves BP, Kier AB, Ball JM, Schroeder F . Sterol carrier protein-2 directly interacts with caveolin-1 in vitro and in vivo . Biochemistry . 43 . 23 . 7288–306 . June 2004 . 15182174 . 10.1021/bi035914n .
25. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP . Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins . The Journal of Biological Chemistry . 272 . 10 . 6525–33 . March 1997 . 9045678 . 10.1074/jbc.272.10.6525 . free .