Linked Life Data

11948419

Source:http://linkedlifedata.com/resource/pubmed/id/11948419

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2002-4-11
pubmed:abstractText
The tumor suppressor gene, MMAC/PTEN, has phosphatase, C2, and PDZ-binding domains as well as potential sites of regulation by phosphorylation, including tyrosine phosphorylation, which may contribute to its ability to modulate cell growth and viability. Several obvious and significant motifs were found in MMAC/PTEN, including most notably, a catalytic domain of tyrosine phosphatase (IHCxxGxxRS/T) and several potential tyrosine phosphorylation sites. To examine the functional significance of tyrosine phosphorylation of MMAC/PTEN, retroviral constructs were generated with mutations at two putative tyrosine phosphorylation sites (Y240A/Y240F and Y315A/Y315F). Stable expression of wild-type MMAC/PTEN in U251 human glioma cells (which do not normally produce a functional MMAC/PTEN gene product) resulted in a significant reduction of tumor growth in nude mice, decreased growth rate, saturation density, and colony formation in vitro, as well as dephosphorylation of D3-phosphorylated phosphatidylinositols (PtdIns) in vitro. Mutation of Y240 or Y315 to either alanine or phenylalanine abrogated the ability of MMAC/PTEN to alter growth rate, saturation density, and colony formation in vitro. The ability of MMAC/PTEN to limit tumor growth in nude mice was markedly decreased but not abrogated by mutation of Y240 or Y315 to alanine. Thus, Y240 and Y315 are required for MMAC/PTEN to decrease tumor growth in vitro and in vivo. In contrast to wild-type MMAC/PTEN, mutant MMAC/PTEN containing Y240A or Y315A was unable to dephosphorylate D3-phosphorylated PtdIns in vitro. Thus, Y240A and Y315A are involved in the ability of MMAC/PTEN to dephosphorylate PtdIns and regulate tumor cell growth in vitro and in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2357-64
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11948419-Amino Acid Motifs, pubmed-meshheading:11948419-Animals, pubmed-meshheading:11948419-Binding Sites, pubmed-meshheading:11948419-Catalytic Domain, pubmed-meshheading:11948419-Cell Division, pubmed-meshheading:11948419-Central Nervous System Neoplasms, pubmed-meshheading:11948419-Genes, Tumor Suppressor, pubmed-meshheading:11948419-Glioma, pubmed-meshheading:11948419-Humans, pubmed-meshheading:11948419-Kinetics, pubmed-meshheading:11948419-Mice, pubmed-meshheading:11948419-Mice, Nude, pubmed-meshheading:11948419-Mutation, pubmed-meshheading:11948419-Neoplasms, pubmed-meshheading:11948419-PTEN Phosphohydrolase, pubmed-meshheading:11948419-Phosphoric Monoester Hydrolases, pubmed-meshheading:11948419-Phosphotyrosine, pubmed-meshheading:11948419-Protein Structure, Tertiary, pubmed-meshheading:11948419-Sequence Analysis, Protein, pubmed-meshheading:11948419-Tumor Cells, Cultured, pubmed-meshheading:11948419-Tumor Suppressor Proteins
pubmed:year
2002
pubmed:articleTitle
Motif analysis of the tumor suppressor gene MMAC/PTEN identifies tyrosines critical for tumor suppression and lipid phosphatase activity.
pubmed:affiliation
Department of Neuro-Oncology, Box 100, The Brain Tumor Center, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't