| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, June 12, 1996, and in revised form, August 27, 1996)
From the Whitehead Institute for Biomedical Research,
Cambridge, Massachusetts 02142-1479
Caveolae are plasma membrane specializations
present in most cell types. Caveolin, a 22-kDa integral membrane
protein, is a principal structural and regulatory component of caveolae
membranes. Previous studies have demonstrated that caveolin co-purifies
with lipid modified signaling molecules, including G
Volume 271, Number 46,
Issue of November 15, 1996
pp. 29182-29190
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Subunits, and H-Ras Share
a Common Membrane-anchored Scaffolding Protein, Caveolin
CAVEOLIN BINDING NEGATIVELY REGULATES THE AUTO-ACTIVATION OF Src
TYROSINE KINASES
subunits, H-Ras, c-Src, and other related Src family tyrosine kinases.
In addition, it has been shown that caveolin interacts directly with G subunits and H-Ras, preferentially recognizing the
inactive conformation of these molecules. However, it is
not known whether caveolin interacts directly or indirectly with Src
family tyrosine kinases. Here, we examine the structural and functional
interaction of caveolin with Src family tyrosine kinases. Caveolin was
recombinantly expressed as a glutathione S-transferase
fusion. Using an established in vitro binding assay, we
find that caveolin interacts with wild-type Src (c-Src) but does not
form a stable complex with mutationally activated Src (v-Src). Thus, it
appears that caveolin prefers the inactive conformation of
Src. Deletion mutagenesis indicates that the Src-interacting domain of
caveolin is located within residues 82-101, a cytosolic
membrane-proximal region of caveolin. A caveolin peptide derived from
this region (residues 82-101) functionally suppressed the
auto-activation of purified recombinant c-Src tyrosine kinase and Fyn,
a related Src family tyrosine kinase. We further analyzed the effect of
caveolin on c-Src activity in vivo by transiently
co-expressing full-length caveolin and c-Src tyrosine kinase in 293T
cells. Co-expression with caveolin dramatically suppressed the tyrosine
kinase activity of c-Src as measured via an immune complex kinase
assay. Thus, it appears that caveolin structurally and functionally
interacts with wild-type c-Src via caveolin residues 82-101. Besides
interacting with Src family kinases, this cytosolic caveolin domain
(residues 82-101) has the following unique features. First, it is
required to form multivalent homo-oligomers of caveolin. Second, it
interacts with G-protein 
-subunits and down-regulates their GTPase
activity. Third, it binds to wild-type H-Ras. Fourth, it is
membrane-proximal, suggesting that it may be involved in other
potential protein-protein interactions. Thus, we have termed this
20-amino acid stretch of caveolin residues the caveolin scaffolding
domain.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Monaghan-Benson, C. C. Mastick, and P. J. McKeown-Longo A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR J. Cell Sci., November 15, 2008; 121(22): 3693 - 3703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Palozza, R. Sestito, N. Picci, P. Lanza, G. Monego, and F. O. Ranelletti The sensitivity to {beta}-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells Carcinogenesis, November 1, 2008; 29(11): 2153 - 2161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Anderson and J. Borlak Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis Pharmacol. Rev., September 1, 2008; 60(3): 311 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Veracini, V. Simon, V. Richard, B. Schraven, V. Horejsi, S. Roche, and C. Benistant The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 J. Cell Biol., August 11, 2008; 182(3): 603 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zheng, J. Chu, Y. Qiu, H. H. Loh, and P.-Y. Law Agonist-selective signaling is determined by the receptor location within the membrane domains PNAS, July 8, 2008; 105(27): 9421 - 9426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. L. Gervasio, N. P. Whitehead, E. W. Yeung, W. D. Phillips, and D. G. Allen TRPC1 binds to caveolin-3 and is regulated by Src kinase - role in Duchenne muscular dystrophy J. Cell Sci., July 1, 2008; 121(13): 2246 - 2255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Maniatis, V. Shinin, D. E. Schraufnagel, S. Okada, S. M. Vogel, A. B. Malik, and R. D. Minshall Increased pulmonary vascular resistance and defective pulmonary artery filling in caveolin-1-/- mice Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L865 - L873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Mostefai, A. Agouni, N. Carusio, M. L. Mastronardi, C. Heymes, D. Henrion, R. Andriantsitohaina, and M. C. Martinez Phosphatidylinositol 3-Kinase and Xanthine Oxidase Regulate Nitric Oxide and Reactive Oxygen Species Productions by Apoptotic Lymphocyte Microparticles in Endothelial Cells J. Immunol., April 1, 2008; 180(7): 5028 - 5035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Le Saux, K. Teeters, S. K. Miyasato, P. R. Hoffmann, O. Bollt, V. Douet, R. V. Shohet, D. H. Broide, and E. K. Tam Down-regulation of Caveolin-1, an Inhibitor of Transforming Growth Factor-{beta} Signaling, in Acute Allergen-induced Airway Remodeling J. Biol. Chem., February 29, 2008; 283(9): 5760 - 5768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zemans and G. P. Downey Role of caveolin-1 in regulation of inflammation: different strokes for different folks Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L175 - L177. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Albinsson, I. Nordstrom, K. Sward, and P. Hellstrand Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall Am J Physiol Cell Physiol, January 1, 2008; 294(1): C271 - C279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gosens, G. L. Stelmack, G. Dueck, M. M. Mutawe, M. Hinton, K. D. McNeill, A. Paulson, S. Dakshinamurti, W. T. Gerthoffer, J. A. Thliveris, et al. Caveolae facilitate muscarinic receptor-mediated intracellular Ca2+ mobilization and contraction in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1406 - L1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Padhan, C. Tanwar, A. Hussain, P. Y. Hui, M. Y. Lee, C. Y. Cheung, J. S. M. Peiris, and S. Jameel Severe acute respiratory syndrome coronavirus Orf3a protein interacts with caveolin J. Gen. Virol., November 1, 2007; 88(11): 3067 - 3077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Sampson, L. M. Davies, R. Barrett-Jolley, N. B. Standen, and C. Dart Angiotensin II-activated protein kinase C targets caveolae to inhibit aortic ATP-sensitive potassium channels Cardiovasc Res, October 1, 2007; 76(1): 61 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Cantiani, M. C. Manara, C. Zucchini, P. De Sanctis, M. Zuntini, L. Valvassori, M. Serra, M. Olivero, M. F. Di Renzo, M. P. Colombo, et al. Caveolin-1 Reduces Osteosarcoma Metastases by Inhibiting c-Src Activity and Met Signaling Cancer Res., August 15, 2007; 67(16): 7675 - 7685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kamishima, T. Burdyga, J. A. Gallagher, and J. M. Quayle Caveolin-1 and caveolin-3 regulate Ca2+ homeostasis of single smooth muscle cells from rat cerebral resistance arteries Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H204 - H214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Carlile-Klusacek and V. Rizzo Endothelial cytoskeletal reorganization in response to PAR1 stimulation is mediated by membrane rafts but not caveolae Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H366 - H375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Humar, R. Fukuzawa, V. Blair, A. Dunbier, H. More, A. Charlton, H. K. Yang, W. H. Kim, A. E. Reeve, I. Martin, et al. Destabilized Adhesion in the Gastric Proliferative Zone and c-Src Kinase Activation Mark the Development of Early Diffuse Gastric Cancer Cancer Res., March 15, 2007; 67(6): 2480 - 2489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-H. Sun, D. C. Flynn, V. Castranova, L. L. Millecchia, A. R. Beardsley, and J. Liu Identification of a Novel Domain at the N Terminus of Caveolin-1 That Controls Rear Polarization of the Protein and Caveolae Formation J. Biol. Chem., March 9, 2007; 282(10): 7232 - 7241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Shajahan, A. Wang, M. Decker, R. D. Minshall, M. C. Liu, and R. Clarke Caveolin-1 Tyrosine Phosphorylation Enhances Paclitaxel-mediated Cytotoxicity J. Biol. Chem., February 23, 2007; 282(8): 5934 - 5943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Song, S. Ge, and J. S. Pachter Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells Blood, February 15, 2007; 109(4): 1515 - 1523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dubroca, X. Loyer, K. Retailleau, G. Loirand, P. Pacaud, O. Feron, J.-L. Balligand, B. I. Levy, C. Heymes, and D. Henrion RhoA activation and interaction with Caveolin-1 are critical for pressure-induced myogenic tone in rat mesenteric resistance arteries Cardiovasc Res, January 1, 2007; 73(1): 190 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-P. Chong, A. S. Chan, K.-C. Chan, N. A. Williamson, E. C. Lerner, T. E. Smithgall, J. D. Bjorge, D. J. Fujita, A. W. Purcell, G. Scholz, et al. C-terminal Src Kinase-homologous Kinase (CHK), a Unique Inhibitor Inactivating Multiple Active Conformations of Src Family Tyrosine Kinases J. Biol. Chem., November 3, 2006; 281(44): 32988 - 32999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Remillard and J. X.-J. Yuan Transient Receptor Potential Channels and Caveolin-1: Good Friends in Tight Spaces Mol. Pharmacol., October 1, 2006; 70(4): 1151 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Veracini, M. Franco, A. Boureux, V. Simon, S. Roche, and C. Benistant Two distinct pools of Src family tyrosine kinases regulate PDGF-induced DNA synthesis and actin dorsal ruffles J. Cell Sci., July 15, 2006; 119(14): 2921 - 2934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Schachter, Y. Du, A. Lin, and K. A. Gallo Dynamic Positive Feedback Phosphorylation of Mixed Lineage Kinase 3 by JNK Reversibly Regulates Its Distribution to Triton-soluble Domains J. Biol. Chem., July 14, 2006; 281(28): 19134 - 19144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhao, H. H. Loh, and P. Y. Law Adenylyl Cyclase Superactivation Induced by Long-Term Treatment with Opioid Agonist Is Dependent on Receptor Localized within Lipid Rafts and Is Independent of Receptor Internalization Mol. Pharmacol., April 1, 2006; 69(4): 1421 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Manara, G. Bernard, P.-L. Lollini, P. Nanni, M. Zuntini, L. Landuzzi, S. Benini, G. Lattanzi, M. Sciandra, M. Serra, et al. CD99 Acts as an Oncosuppressor in Osteosarcoma Mol. Biol. Cell, April 1, 2006; 17(4): 1910 - 1921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. O. D. Achcar, Y. Demura, P. R. Rai, L. Taraseviciene-Stewart, M. Kasper, N. F. Voelkel, and C. D. Cool Loss of Caveolin and Heme Oxygenase Expression in Severe Pulmonary Hypertension Chest, March 1, 2006; 129(3): 696 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Levin, J. G. Coroneus, M. J. Cocco, and G. A. Weiss Exploring the interaction between the protein kinase A catalytic subunit and caveolin-1 scaffolding domain with shotgun scanning, oligomer complementation, NMR, and docking Protein Sci., March 1, 2006; 15(3): 478 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Feron and J.-L. Balligand Caveolins and the regulation of endothelial nitric oxide synthase in the heart Cardiovasc Res, March 1, 2006; 69(4): 788 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Rahmani APRO4 negatively regulates Src tyrosine kinase activity in PC12 cells J. Cell Sci., February 15, 2006; 119(4): 646 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Konopleva, W. Zhang, Y.-X. Shi, T. McQueen, T. Tsao, M. Abdelrahim, M. F. Munsell, M. Johansen, D. Yu, T. Madden, et al. Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2-overexpressing breast cancer cells. Mol. Cancer Ther., February 1, 2006; 5(2): 317 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rubin, T. C. Murphy, J. Rahnert, H. Song, M. S. Nanes, E. M. Greenfield, H. Jo, and X. Fan Mechanical Inhibition of RANKL Expression Is Regulated by H-Ras-GTPase J. Biol. Chem., January 20, 2006; 281(3): 1412 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Sotgia, T. M. Williams, W. Schubert, F. Medina, C. Minetti, R. G. Pestell, and M. P. Lisanti Caveolin-1 Deficiency (-/-) Conveys Premalignant Alterations in Mammary Epithelia, with Abnormal Lumen Formation, Growth Factor Independence, and Cell Invasiveness Am. J. Pathol., January 1, 2006; 168(1): 292 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Matthews, M. J. Taggart, and M. Westwood Effect of Cholesterol Depletion on Mitogenesis and Survival: The Role of Caveolar and Noncaveolar Domains in Insulin-Like Growth Factor-Mediated Cellular Function Endocrinology, December 1, 2005; 146(12): 5463 - 5473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Miotti, A. Tomassetti, I. Facetti, E. Sanna, V. Berno, and S. Canevari Simultaneous Expression of Caveolin-1 and E-Cadherin in Ovarian Carcinoma Cells Stabilizes Adherens Junctions through Inhibition of src-Related Kinases Am. J. Pathol., November 1, 2005; 167(5): 1411 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Toselli, G. Biella, V. Taglietti, E. Cazzaniga, and M. Parenti Caveolin-1 Expression and Membrane Cholesterol Content Modulate N-Type Calcium Channel Activity in NG108-15 Cells Biophys. J., October 1, 2005; 89(4): 2443 - 2457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schwencke, A. Schmeisser, C. Walter, R. Wachter, S. Pannach, B. Weck, R. C. Braun-Dullaeus, M. Kasper, and R. H. Strasser Decreased caveolin-1 in atheroma: Loss of antiproliferative control of vascular smooth muscle cells in atherosclerosis Cardiovasc Res, October 1, 2005; 68(1): 128 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chao, K. L. Ives, E. Goluszko, A. A. Kolokoltsov, R. A. Davey, C. M. Townsend Jr., and M. R. Hellmich Src Regulates Constitutive Internalization and Rapid Resensitization of a Cholecystokinin 2 Receptor Splice Variant J. Biol. Chem., September 30, 2005; 280(39): 33368 - 33373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nonami, T. Taketomi, A. Kimura, K. Saeki, H. Takaki, T. Sanada, K. Taniguchi, M. Harada, R. Kato, and A. Yoshimura The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1 Genes Cells, September 1, 2005; 10(9): 887 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Nixon, J. Wegner, C. Ferguson, P.-F. Mery, J. F. Hancock, P. D. Currie, B. Key, M. Westerfield, and R. G. Parton Zebrafish as a model for caveolin-associated muscle disease; caveolin-3 is required for myofibril organization and muscle cell patterning Hum. Mol. Genet., July 1, 2005; 14(13): 1727 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sies, W. Stahl, and A. Sevanian Nutritional, Dietary and Postprandial Oxidative Stress J. Nutr., May 1, 2005; 135(5): 969 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Schutzer, J. F. Reed, and S. L. Mader Decline in caveolin-1 expression and scaffolding of G protein receptor kinase-2 with age in Fischer 344 aortic vascular smooth muscle Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2457 - H2464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Bellott, K. C. Patel, and T. J. Burkholder Reduction of caveolin-3 expression does not inhibit stretch-induced phosphorylation of ERK2 in skeletal muscle myotubes J Appl Physiol, April 1, 2005; 98(4): 1554 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Williams and M. P. Lisanti Caveolin-1 in oncogenic transformation, cancer, and metastasis Am J Physiol Cell Physiol, March 1, 2005; 288(3): C494 - C506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Labrecque, C. Nyalendo, S. Langlois, Y. Durocher, C. Roghi, G. Murphy, D. Gingras, and R. Beliveau Src-mediated Tyrosine Phosphorylation of Caveolin-1 Induces Its Association with Membrane Type 1 Matrix Metalloproteinase J. Biol. Chem., December 10, 2004; 279(50): 52132 - 52140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Williams, F. Medina, I. Badano, R. B. Hazan, J. Hutchinson, W. J. Muller, N. G. Chopra, P. E. Scherer, R. G. Pestell, and M. P. Lisanti Caveolin-1 Gene Disruption Promotes Mammary Tumorigenesis and Dramatically Enhances Lung Metastasis in Vivo: ROLE OF CAV-1 IN CELL INVASIVENESS AND MATRIX METALLOPROTEINASE (MMP-2/9) SECRETION J. Biol. Chem., December 3, 2004; 279(49): 51630 - 51646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. NAVARRO, B. ANAND-APTE, and M.-O. PARAT A role for caveolae in cell migration FASEB J, December 1, 2004; 18(15): 1801 - 1811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, V. G. Brunton, H. R. Burgar, L. M. Wheldon, and J. K. Heath FRS2-dependent SRC activation is required for fibroblast growth factor receptor-induced phosphorylation of Sprouty and suppression of ERK activity J. Cell Sci., December 1, 2004; 117(25): 6007 - 6017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Fleet Rapid, Membrane-Initiated Actions of 1,25 Dihydroxyvitamin D: What Are They and What Do They Mean? J. Nutr., December 1, 2004; 134(12): 3215 - 3218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Shajahan, C. Tiruppathi, A. V. Smrcka, A. B. Malik, and R. D. Minshall G{beta}{gamma} Activation of Src Induces Caveolae-mediated Endocytosis in Endothelial Cells J. Biol. Chem., November 12, 2004; 279(46): 48055 - 48062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
