Literature summary for 3.1.3.67 extracted from

Rahdar, M.; Inoue, T.; Meyer, T.; Zhang, J.; Vazquez, F.; Devreotes, P.N.
A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN (2009), Proc. Natl. Acad. Sci. USA, 106, 480-485.

Application

Application	Comment	Organism
drug development	This study is a direct evidence for a model in which PTEN switches between open and closed states and phosphorylation favors the closed conformation, thereby regulating localization and function. Small molecules targeting these interactions can potentially serve as therapeutic agents in antagonizing Ras or phosphoinositide 3-kinase-driven tumors.	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
PTEN-null U87 cells are transiently transfected with either wild-type PTEN-green fluorescent protein or PTEN-alanine substituted-green fluorescent protein. U87 cells expressing PH-AKT1-green fluorescent protein are co-transfected with either wildtype PTEN or PTEN-alanine substituted enzyme. Whereas two cells co-expressing wild-type PTEN and PH-AKT1-green fluorescent protein fails to respond to epidermal growth factor stimulation, all PTEN-alanine substituted proteins co-transfected cells fail to respond. HeLa cells are transiently co-transfected with cyan fluorescent protein-FKBP-inositol polyphosphate-5-phosphatase and PTEN-C124S-alanine substituted-yellow fluorescent protein. Expression of PTEN-C124Salanine substituted-yellow fluorescent protein in HeLa cells.	Homo sapiens

Cloned (Comment)

Organism

PTEN-null U87 cells are transiently transfected with either wild-type PTEN-green fluorescent protein or PTEN-alanine substituted-green fluorescent protein. U87 cells expressing PH-AKT1-green fluorescent protein are co-transfected with either wildtype PTEN or PTEN-alanine substituted enzyme. Whereas two cells co-expressing wild-type PTEN and PH-AKT1-green fluorescent protein fails to respond to epidermal growth factor stimulation, all PTEN-alanine substituted proteins co-transfected cells fail to respond. HeLa cells are transiently co-transfected with cyan fluorescent protein-FKBP-inositol polyphosphate-5-phosphatase and PTEN-C124S-alanine substituted-yellow fluorescent protein. Expression of PTEN-C124Salanine substituted-yellow fluorescent protein in HeLa cells.

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
C124S	mutant PTEN-C124S-A4-YFP lacks lipid and protein phosphatase activity, great localization to the plasma membrane than other mutants	Homo sapiens
DELTA352-403	truncated enzyme binds strongly to the plasma membrane, an effect that is reversed by co-expression of the remainder of the molecule, PTEN 352-403	Homo sapiens
S380A	PTEN-green fluorescent protein mutant shows significant localization to the plasma membrane, the effect requires no catalytic activity	Homo sapiens
S383A	PTEN-green fluorescent protein mutant shows significant localization to the plasma membrane, the effect requires no catalytic activity	Homo sapiens
T382A	PTEN-green fluorescent protein mutant shows significant localization to the plasma membrane, the effect requires no catalytic activity	Homo sapiens
T385A	PTEN-green fluorescent protein mutant shows significant localization to the plasma membrane, the effect requires no catalytic activity	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
H2O2	H2O2 reversibly inhibits PTEN activity by covalently linking Cys-71 to Cys-124, inhibition partially reverses by inclusion of 100 mM dithiothreitol to the buffer	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-
nucleus	-	Homo sapiens	5634	-
plasma membrane	although the main substrate of PTEN is at the plasma membrane, the enzyme is mainly found in cytosol and the nucleus, but a small fraction is dynamically associated with the inner face of the plasma membrane	Homo sapiens	5886	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
additional information	Homo sapiens	PTEN, one of the most important tumor suppressors, must associate with the plasma membrane to maintain appropriate steady-state levels of phosphatidylinositol 3,4,5-triphosphate	?	-	?
additional information	Homo sapiens	the membrane binding of PTEN requires phosphatidylinositol 4,5-bisphosphate	?	-	?
phosphatidylinositol 3,4,5-triphosphate + H2O	Homo sapiens	-	phosphatidylinositol 4,5-bisphosphate + phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
phosphoprotein	C-terminal 51 amino acids contains a cluster of phosphorylation sites which regulates protein stability and function in cells, a phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN, phosphorylation of the C-terminal cluster has an inhibitory effect on membrane association and activity	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
HEK-293 cell	-	Homo sapiens	-
HEK-293T cell	human embryonic kidney cell	Homo sapiens	-
HeLa cell	-	Homo sapiens	-
U-87MG cell	glioblastoma-astrocytoma, epithelial-like cell line	Homo sapiens	-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
additional information	-	activity of PTEN is dependent on extent of membrane binding, phosphorylation of the C-terminal cluster has an inhibitory effect on membrane association and activity	Homo sapiens
additional information	-	alanine substituted PTEN is 7fold more active than wildtype PTEN	Homo sapiens
additional information	-	PTEN cellular activity is proportional to the extent of membrane association	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	PTEN, one of the most important tumor suppressors, must associate with the plasma membrane to maintain appropriate steady-state levels of phosphatidylinositol 3,4,5-triphosphate	Homo sapiens	?	-	?
additional information	the membrane binding of PTEN requires phosphatidylinositol 4,5-bisphosphate	Homo sapiens	?	-	?
phosphatidylinositol 3,4,5-triphosphate + H2O	-	Homo sapiens	phosphatidylinositol 4,5-bisphosphate + phosphate	-	?

Synonyms

Synonyms	Comment	Organism
phosphatase and tensin homologue deleted on chromosome 10	-	Homo sapiens
PI 3-phosphatase	-	Homo sapiens
PTEN	-	Homo sapiens