Caveolin 1

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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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

References

  1. Fra AM, Mastroianni N, Mancini M, Pasqualetto E, Sitia R (March 1999). "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. doi:10.1006/geno.1998.5723. PMID 10087206.
  2. "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 (June 1995). "Evidence for a regulated interaction between heterotrimeric G proteins and caveolin". The Journal of Biological Chemistry. 270 (26): 15693–701. doi:10.1074/jbc.270.26.15693. PMID 7797570.
  4. 4.0 4.1 Li S, Couet J, Lisanti MP (November 1996). "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. doi:10.1074/jbc.271.46.29182. PMID 8910575.
  5. Li S, Song KS, Lisanti MP (January 1996). "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. doi:10.1074/jbc.271.1.568. PMID 8550621.
  6. Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP (March 2001). "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. doi:10.1074/jbc.M008340200. PMID 11102446.
  7. García-Cardeña G, Fan R, Stern DF, Liu J, Sessa WC (November 1996). "Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin-1". The Journal of Biological Chemistry. 271 (44): 27237–40. doi:10.1074/jbc.271.44.27237. PMID 8910295.
  8. Lu ML, Schneider MC, Zheng Y, Zhang X, Richie JP (April 2001). "Caveolin-1 interacts with androgen receptor. A positive modulator of androgen receptor mediated transactivation". The Journal of Biological Chemistry. 276 (16): 13442–51. doi:10.1074/jbc.M006598200. PMID 11278309.
  9. Ikezu T, Trapp BD, Song KS, Schlegel A, Lisanti MP, Okamoto T (April 1998). "Caveolae, plasma membrane microdomains for alpha-secretase-mediated processing of the amyloid precursor protein". The Journal of Biological Chemistry. 273 (17): 10485–95. doi:10.1074/jbc.273.17.10485. PMID 9553108.
  10. Schubert AL, Schubert W, Spray DC, Lisanti MP (May 2002). "Connexin family members target to lipid raft domains and interact with caveolin-1". Biochemistry. 41 (18): 5754–64. doi:10.1021/bi0121656. PMID 11980479.
  11. Felley-Bosco E, Bender FC, Courjault-Gautier F, Bron C, Quest AF (December 2000). "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. Bibcode:2000PNAS...9714334F. doi:10.1073/pnas.250406797. PMC 18919. PMID 11114180.
  12. Couet J, Sargiacomo M, Lisanti MP (November 1997). "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. doi:10.1074/jbc.272.48.30429. PMID 9374534.
  13. Yamaguchi T, Murata Y, Fujiyoshi Y, Doi T (April 2003). "Regulated interaction of endothelin B receptor with caveolin-1". European Journal of Biochemistry. 270 (8): 1816–27. doi:10.1046/j.1432-1033.2003.03544.x. PMID 12694195.
  14. 14.0 14.1 Yamamoto M, Toya Y, Jensen RA, Ishikawa Y (March 1999). "Caveolin is an inhibitor of platelet-derived growth factor receptor signaling". Experimental Cell Research. 247 (2): 380–8. doi:10.1006/excr.1998.4379. PMID 10066366.
  15. Liou JY, Deng WG, Gilroy DW, Shyue SK, Wu KK (September 2001). "Colocalization and interaction of cyclooxygenase-2 with caveolin-1 in human fibroblasts". The Journal of Biological Chemistry. 276 (37): 34975–82. doi:10.1074/jbc.M105946200. PMID 11432874.
  16. Feng X, Gaeta ML, Madge LA, Yang JH, Bradley JR, Pober JS (March 2001). "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. doi:10.1074/jbc.M007116200. PMID 11112773.
  17. Cao H, Courchesne WE, Mastick CC (March 2002). "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. doi:10.1074/jbc.C100661200. PMID 11805080.
  18. Schlegel A, Wang C, Pestell RG, Lisanti MP (October 2001). "Ligand-independent activation of oestrogen receptor alpha by caveolin-1". The Biochemical Journal. 359 (Pt 1): 203–10. doi:10.1042/0264-6021:3590203. PMC 1222136. PMID 11563984.
  19. Breuza L, Corby S, Arsanto JP, Delgrossi MH, Scheiffele P, Le Bivic A (December 2002). "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. doi:10.1242/jcs.00130. PMID 12414992.
  20. Scherer PE, Lewis RY, Volonte D, Engelman JA, Galbiati F, Couet J, Kohtz DS, van Donselaar E, Peters P, Lisanti MP (November 1997). "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. doi:10.1074/jbc.272.46.29337. PMID 9361015.
  21. Zheng X, Bollinger Bollag W (December 2003). "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. doi:10.1111/j.1523-1747.2003.12614.x. PMID 14675200.
  22. Czarny M, Fiucci G, Lavie Y, Banno Y, Nozawa Y, Liscovitch M (February 2000). "Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains". FEBS Letters. 467 (2–3): 326–32. doi:10.1016/S0014-5793(00)01174-1. PMID 10675563.
  23. Vargas L, Nore BF, Berglof A, Heinonen JE, Mattsson PT, Smith CI, Mohamed AJ (March 2002). "Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx". The Journal of Biological Chemistry. 277 (11): 9351–7. doi:10.1074/jbc.M108537200. PMID 11751885.
  24. Zhou M, Parr RD, Petrescu AD, Payne HR, Atshaves BP, Kier AB, Ball JM, Schroeder F (June 2004). "Sterol carrier protein-2 directly interacts with caveolin-1 in vitro and in vivo". Biochemistry. 43 (23): 7288–306. doi:10.1021/bi035914n. PMID 15182174.
  25. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP (March 1997). "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. doi:10.1074/jbc.272.10.6525. PMID 9045678.

Further reading