TY - JOUR
T1 - Crystal structure of the PTEN tumor suppressor
T2 - Implications for its phosphoinositide phosphatase activity and membrane association
AU - Lee, Jie Oh
AU - Yang, Haijuan
AU - Georgescu, Maria Magdalena
AU - Cristofano, Antonio Di
AU - Maehama, Tomohiko
AU - Shi, Yigong
AU - Dixon, Jack E.
AU - Pandolfi, Pier
AU - Pavletich, Nikola P.
N1 - Funding Information:
We thank S. Geromanos and H. Erdjument-Bromage of the Sloan-Kettering Microchemistry Facility for N-terminal sequence and mass spectroscopic analyses; the staff of the Cornell High Energy Synchrotron Source (MacChess) for help with data collection; T. Weber for advice about the lipid binding assay; and C. Murray for administrative help. This work was supported by the Howard Hughes Medical Institute, the National Institutes of Health, the Dewitt Wallace Foundation, the Samuel and May Rudin Foundation, and the Walther Cancer Institute. M. M. G. was supported by fellowships from the Medical Research Council of Canada and the National Cancer Institute (CA09673). P. P. is a scholar of the Leukemia Society of America.
PY - 1999/10/29
Y1 - 1999/10/29
N2 - The PTEN tumor suppressor is mutated in diverse human cancers and in hereditary cancer predisposition syndromes. PTEN is a phosphatase that can act on both polypeptide and phosphoinositide substrates in vitro. The PTEN structure reveals a phosphatase domain that is similar to protein phosphatases but has an enlarged active site important for the accommodation of the phosphoinositide substrate. The structure also reveals that PTEN has a C2 domain. The PTEN C2 domain binds phospholipid membranes in vitro, and mutation of basic residues that could mediate this reduces PTEN's membrane affinity and its ability to suppress the growth of glioblastoma tumor cells. The phosphatase and C2 domains associate across an extensive interface, suggesting that the C2 domain may serve to productively position the catalytic domain on the membrane.
AB - The PTEN tumor suppressor is mutated in diverse human cancers and in hereditary cancer predisposition syndromes. PTEN is a phosphatase that can act on both polypeptide and phosphoinositide substrates in vitro. The PTEN structure reveals a phosphatase domain that is similar to protein phosphatases but has an enlarged active site important for the accommodation of the phosphoinositide substrate. The structure also reveals that PTEN has a C2 domain. The PTEN C2 domain binds phospholipid membranes in vitro, and mutation of basic residues that could mediate this reduces PTEN's membrane affinity and its ability to suppress the growth of glioblastoma tumor cells. The phosphatase and C2 domains associate across an extensive interface, suggesting that the C2 domain may serve to productively position the catalytic domain on the membrane.
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U2 - 10.1016/S0092-8674(00)81663-3
DO - 10.1016/S0092-8674(00)81663-3
M3 - Article
C2 - 10555148
AN - SCOPUS:0033615538
SN - 0092-8674
VL - 99
SP - 323
EP - 334
JO - Cell
JF - Cell
IS - 3
ER -
