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2015 ; 77-78
(ä): 119-24
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Engineering PTEN function: membrane association and activity
#MMPMID25448479
Yang JM
; Nguyen HN
; Sesaki H
; Devreotes PN
; Iijima M
Methods
2015[May]; 77-78
(ä): 119-24
PMID25448479
show ga
Many tumors are associated with deficiency of the tumor suppressor, PTEN, a PIP3
phosphatase that turns off PIP3 signaling. The major site of PTEN action is the
plasma membrane, where PIP3 is produced by PI3 kinases. However, the mechanism
and functional importance of PTEN membrane recruitment are poorly defined. Using
the heterologous expression system in which human PTEN is expressed in
Dictyostelium discoideum, we defined the molecular mechanisms that regulate the
membrane-binding site through inhibitory interactions with the phosphorylated
C-terminal tail. In addition, we potentiated mechanisms that mediate PTEN
membrane association and engineered an enhanced PTEN with increased tumor
suppressor functions. Moreover, we identified a new class of cancer-associated
PTEN mutations that are specifically defective in membrane association. In this
review, we summarize recent advances in PTEN-membrane interactions and methods
useful in addressing PTEN function.