Oestrogen-mediated tyrosine phosphorylation of caveolin-1 and its effect on the oestrogen receptor localisation: an in vivo study.
Recently, it has been shown that 17beta estradiol (E2) induces a rapid and transient activation of the Src ERK phosphorylation cascade: a clear indication that the alpha oestrogen receptor (ERalpha) is able to associate with the plasma membrane. Increasing evidence suggests that caveolae, which are caveolin-1 containing, highly hydrophobic membrane domains, play an important role in E2 induced signal transduction. Caveolae can accumulate signalling molecules preferentially; thus, they may have a regulatory role in signalling processes. Results from previous experiments have shown that E2 treatment decreased the number of surface connected caveolae significantly in uterine smooth muscle cells and also downregulated the expression of caveolin-1. In addition to providing further evidence that ERalpha interacts with caveolin/caveolae in uterine smooth muscle cells, this study also shows that the interaction between caveolin-1 and ERalpha is actually facilitated by E2. One of the signal transduction components found to accumulate in caveolae is Src kinase in an amount that increases simultaneously with increases in the amount of ERalpha. Upon E2 treatment, Src kinase is tyrosine phosphorylated, which, in turn, stimulates Src kinase to phosphorylate caveolin-1. Phosphorylation of caveolin-1 can drive caveolae to pinch off from the plasma membrane, thereby decreasing the amount of plasma membrane-associated caveolin-1. This loss of caveolin/caveolae activates the signal cascade that triggers cell proliferation.
Kiss
Anna L
AL
Department of Human Morphology and Developmental Biology, Semmelweis University Budapest, H-1450 Budapest, Tuzoltó u. 58, Hungary. KissA@ana2.sote.hu
Turi
Agnes
A
Müllner
Nándor
N
Kovács
Eniko
E
Botos
Erzsébet
E
Greger
Anikó
A
D000818:Animals; D021941:Caveolae / Q000737:chemistry* / Q000201:enzymology / Q000502:physiology; D051242:Caveolin 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D049109:Cell Proliferation; D015536:Down-Regulation / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000502:physiology*; D014599:Uterus / Q000737:chemistry / Q000201:enzymology / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism
D051242:Caveolin 1; D047628:Estrogen Receptor alpha; D014443:Tyrosine; D004958:Estradiol; D019061:src-Family Kinases