PTEN and myotubularin phosphatases: from 3-phosphoinositide dephosphorylation to disease.

The phosphatase and tensin homolog deleted on chromosome ten (PTEN) and myotubularin (MTM1) represent subfamilies of protein tyrosine phosphatases whose principal physiological substrates are D3-phosphorylated inositol phospholipids. As lipid phosphatases, PTEN- and MTM1-related (MTMR) proteins dephosphorylate the products of phosphoinositide 3-kinases and antagonize downstream effectors that utilize 3-phosphoinositides as ligands for protein targeting domains or allosteric activation. Here, we describe the cellular mechanisms of PTEN and MTMR function and their role in the etiology of cancer and other human diseases.

[1]  G. Ruvkun,et al.  The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. , 1998, Molecular cell.

[2]  P. Huie,et al.  Male infertility, impaired spermatogenesis, and azoospermia in mice deficient for the pseudophosphatase Sbf1. , 2002, The Journal of clinical investigation.

[3]  N. Bottini,et al.  Negative Feedback Regulation of the Tumor Suppressor PTEN by Phosphoinositide-Induced Serine Phosphorylation1 , 2002, The Journal of Immunology.

[4]  L. Liaubet,et al.  Functional redundancy in the myotubularin family. , 2002, Biochemical and biophysical research communications.

[5]  J. Dixon,et al.  PTEN and myotubularin phosphoinositide phosphatases: bringing bioinformatics to the lab bench. , 2001, Current opinion in cell biology.

[6]  E. Hafen,et al.  Living with Lethal PIP3 Levels: Viability of Flies Lacking PTEN Restored by a PH Domain Mutation in Akt/PKB , 2002, Science.

[7]  C. Eng,et al.  Protean PTEN: form and function. , 2002, American journal of human genetics.

[8]  Richard A. Firtel,et al.  Spatial and Temporal Regulation of 3-Phosphoinositides by PI 3-Kinase and PTEN Mediates Chemotaxis , 2002, Cell.

[9]  C. Kahn,et al.  Regulation of Myocardial Contractility and Cell Size by Distinct PI3K-PTEN Signaling Pathways , 2002, Cell.

[10]  B. Hemmings,et al.  Ten years of protein kinase B signalling: a hard Akt to follow. , 2001, Trends in biochemical sciences.

[11]  I. Pass,et al.  Tumor suppressor and anti-inflammatory actions of PPARγ agonists are mediated via upregulation of PTEN , 2001, Current Biology.

[12]  G. Mills,et al.  Motif analysis of the tumor suppressor gene MMAC/PTEN identifies tyrosines critical for tumor suppression and lipid phosphatase activity , 2002, Oncogene.

[13]  J. Mandel,et al.  The myotubularin family: from genetic disease to phosphoinositide metabolism. , 2001, Trends in genetics : TIG.

[14]  T. Mak,et al.  Regulation of PTEN transcription by p53. , 2001, Molecular cell.

[15]  C. Ross,et al.  Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[16]  A. Berns,et al.  PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. , 2002, Development.

[17]  G S Taylor,et al.  PTEN and myotubularin: novel phosphoinositide phosphatases. , 2001, Annual review of biochemistry.

[18]  Yan Wu,et al.  Interaction of the Tumor Suppressor PTEN/MMAC with a PDZ Domain of MAGI3, a Novel Membrane-associated Guanylate Kinase* , 2000, The Journal of Biological Chemistry.

[19]  Tomohiko Maehama,et al.  Crystal Structure of the PTEN Tumor Suppressor Implications for Its Phosphoinositide Phosphatase Activity and Membrane Association , 1999, Cell.

[20]  D. Goberdhan,et al.  Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. , 1999, Genes & development.

[21]  C. Borland,et al.  The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[22]  G. Raposo,et al.  Characterization of MTMR3 an inositol lipid 3-phosphatase with novel substrate specificity , 2001, Current Biology.

[23]  J. Dixon,et al.  Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[24]  B. Monia,et al.  Specific inhibition of PTEN expression reverses hyperglycemia in diabetic mice. , 2002, Diabetes.

[25]  J. Whisstock,et al.  Characterization of an adapter subunit to a phosphatidylinositol (3)P 3-phosphatase: Identification of a myotubularin-related protein lacking catalytic activity , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  T. Mustelin,et al.  The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling , 2001, Nature Cell Biology.

[27]  Kenneth M. Yamada,et al.  Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. , 2001, Journal of cell science.

[28]  P. Devreotes,et al.  Tumor Suppressor PTEN Mediates Sensing of Chemoattractant Gradients , 2002, Cell.

[29]  Carlos Cordon-Cardo,et al.  Pten is essential for embryonic development and tumour suppression , 1998, Nature Genetics.

[30]  S. Klauck,et al.  A gene mutated in X–linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast , 1996, Nature Genetics.

[31]  Tomohiko Maehama,et al.  The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate* , 1998, The Journal of Biological Chemistry.

[32]  Soo-A Kim,et al.  Myotubularin and MTMR2, Phosphatidylinositol 3-Phosphatases Mutated in Myotubular Myopathy and Type 4B Charcot-Marie-Tooth Disease* , 2002, The Journal of Biological Chemistry.

[33]  Aldo Quattrone,et al.  Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2 , 2000, Nature Genetics.

[34]  William R. Sellers,et al.  Phosphorylation of the PTEN Tail Acts as an Inhibitory Switch by Preventing Its Recruitment into a Protein Complex* , 2001, The Journal of Biological Chemistry.

[35]  W. K. Alfred Yung,et al.  Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers , 1997, Nature Genetics.

[36]  J. Dixon,et al.  PTEN Protects p53 from Mdm2 and Sensitizes Cancer Cells to Chemotherapy* , 2002, The Journal of Biological Chemistry.

[37]  M. Waterfield,et al.  Synthesis and function of 3-phosphorylated inositol lipids. , 2001, Annual review of biochemistry.

[38]  C. Downes,et al.  TPIP: a novel phosphoinositide 3-phosphatase. , 2001, The Biochemical journal.

[39]  P. Cullen,et al.  Modular phosphoinositide-binding domains – their role in signalling and membrane trafficking , 2001, Current Biology.

[40]  S. Morrison Pten-uating neural growth , 2002, Nature Medicine.

[41]  M. Wigler,et al.  PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer , 1997, Science.

[42]  E. Hafen,et al.  PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. , 1999, Development.

[43]  M. Wigler,et al.  P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[44]  I. Sutton,et al.  Limb girdle and facial weakness in female carriers of X-linked myotubular myopathy mutations , 2001, Neurology.