The phosphorylation of caveolin-2 on serines 23 and 36 modulates caveolin-1-dependent caveolae formation.
Caveolin-1 and -2 are the two major coat proteins found in plasma membrane caveolae of most of cell types. Here, by using adenoviral transduction of either caveolin-1 or caveolin-2 or both isoforms into cells lacking both caveolins, we demonstrate that caveolin-2 positively regulates caveolin-1-dependent caveolae formation. More importantly, we show that caveolin-2 is phosphorylated in vivo at two serine residues and that the phosphorylation of caveolin-2 is necessary for its actions as a positive regulator of caveolin-1 during organelle biogenesis in prostate cancer cells. Mutation of the primary phosphorylation sites on caveolin-2, serine 23 and 36, reduces the number of plasmalemma-attached caveolae and increases the accumulation of noncoated vesicles, but does not affect trafficking of caveolin-2, interaction with caveolin-1 or its biophysical properties. Thus, the phosphorylation of caveolin-2 is a novel mechanism to regulate the dynamics of caveolae assembly.
Sowa
Grzegorz
G
Department of Pharmacology, Vascular Cell Signaling and Therapeutics Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Pypaert
Marc
M
Fulton
David
D
Sessa
William C
WC
D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism*
C495540:CAV1 protein, human; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D012694:Serine; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases