Germline PIK3CA and AKT1 Mutations in Cowden and Cowden-like Syndromes

Slides:

Advertisements

Similar presentations

Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and.

Advertisements

Connexin Mutations in Skin Disease and Hearing Loss David P. Kelsell, Wei-Li Di, Mark J. Houseman The American Journal of Human Genetics Volume 68, Issue.

Functional Analysis of the Neurofibromatosis Type 2 Protein by Means of Disease- Causing Point Mutations Renee P. Stokowski, David R. Cox The American.

Gene Preference in Maple Syrup Urine Disease Mary M. Nellis, Dean J. Danner The American Journal of Human Genetics Volume 68, Issue 1, Pages (January.

Fragile X and X-Linked Intellectual Disability: Four Decades of Discovery Herbert A. Lubs, Roger E. Stevenson, Charles E. Schwartz The American Journal.

Nan-Hyung Kim, Ai-Young Lee Journal of Investigative Dermatology

Volume 124, Issue 7, Pages (June 2003)

Juewon Kim, Hyunjung Choi, Eun-Gyung Cho, Tae R. Lee

Vemurafenib Induces Senescence Features in Melanoma Cells

Jaya Sahni, Andrew M. Scharenberg Cell Metabolism

Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling Yu-Juei Hsu, MD, PhD, Shih-Che Hsu,

Volume 19, Issue 2, Pages (July 2005)

(A) Prdx1−/−MEFs and Prdx1+/+MEFs were stimulated with H2O2 as indicated. (A) Prdx1−/−MEFs and Prdx1+/+MEFs were stimulated with H2O2 as indicated. Protein.

Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling Yu-Juei Hsu, MD, PhD, Shih-Che Hsu,

Phosphatidylinositol 3-Kinase/Akt-Dependent and -Independent Protection Against Apoptosis in Normal Human Melanocytes Masahiro Oka, Akiko Kageyama, Mizuho.

Volume 139, Issue 6, Pages (December 2010)

Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport.

Volume 128, Issue 5, Pages (May 2005)

A Nonsense Mutation in DHTKD1 Causes Charcot-Marie-Tooth Disease Type 2 in a Large Chinese Pedigree Wang-yang Xu, Ming-min Gu, Lian-hua Sun, Wen-ting.

Daisuke Suzuki, Makoto Senoo Journal of Investigative Dermatology

CaMKII inhibition in human primary and pluripotent stem cell-derived chondrocytes modulates effects of TGFβ and BMP through SMAD signaling B. Saitta,

Volume 136, Issue 4, Pages e3 (April 2009)

Green Tea Extract and (−)-Epigallocatechin-3-Gallate Inhibit Mast Cell-Stimulated Type I Collagen Expression in Keloid Fibroblasts via Blocking PI-3K/Akt.

Mutations in PADI6 Cause Female Infertility Characterized by Early Embryonic Arrest Yao Xu, Yingli Shi, Jing Fu, Min Yu, Ruizhi Feng, Qing Sang, Bo Liang,

Andreea M. Bujor, Jaspreet Pannu, Shizhong Bu, Edwin A. Smith, Robin C

Collagen XVII Shedding Suppresses Re-Epithelialization by Directing Keratinocyte Migration and Dampening mTOR Signaling Joanna Jacków, Stefanie Löffek,

Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer Lamis Yehia, Farshad.

Molecular Therapy - Nucleic Acids

Volume 125, Issue 4, Pages (May 2006)

PRL-3 Promotes the Malignant Progression of Melanoma via Triggering Dephosphorylation and Cytoplasmic Localization of NHERF1 Xian-Ying Fang, Ran Song,

Estrogenic regulation of testicular expression of stem cell factor and c-kit: implications in germ cell survival and male fertility Sara Correia, M.S.,

Human RAD50 Deficiency in a Nijmegen Breakage Syndrome-like Disorder

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility Tailai Chen, Yuehong Bian, Xiaoman Liu, Shigang Zhao, Keliang.

Volume 27, Issue 1, Pages (January 2015)

Germline Inactivation of PTEN and Dysregulation of the Phosphoinositol-3-Kinase/Akt Pathway Cause Human Lhermitte-Duclos Disease in Adults Xiao-Ping.

Volume 27, Issue 1, Pages (January 2015)

Song-Hai Shi, Lily Yeh Jan, Yuh-Nung Jan Cell

Overexpression of CD109 in the Epidermis Differentially Regulates ALK1 Versus ALK5 Signaling and Modulates Extracellular Matrix Synthesis in the Skin

Heat Shock Transcription Factor 1 Is a Key Determinant of HCC Development by Regulating Hepatic Steatosis and Metabolic Syndrome Xiongjie Jin, Demetrius.

14-3-3σ Regulates Keratinocyte Proliferation and Differentiation by Modulating Yap1 Cellular Localization Sumitha A.T. Sambandam, Ramesh B. Kasetti,

Volume 16, Issue 12, Pages (December 2009)

TALEN Gene Knockouts Reveal No Requirement for the Conserved Human Shelterin Protein Rap1 in Telomere Protection and Length Regulation Shaheen Kabir,

Homozygous Mutations in WEE2 Cause Fertilization Failure and Female Infertility Qing Sang, Bin Li, Yanping Kuang, Xueqian Wang, Zhihua Zhang, Biaobang.

Cowden Syndrome–Affected Patients with PTEN Promoter Mutations Demonstrate Abnormal Protein Translation Rosemary E. Teresi, Kevin M. Zbuk, Marcus G.

Volume 7, Issue 1, Pages (January 2008)

Exome Sequencing Identifies Autosomal-Dominant SRP72 Mutations Associated with Familial Aplasia and Myelodysplasia Michael Kirwan, Amanda J. Walne, Vincent.

Volume 122, Issue 2, Pages (July 2005)

Erratum The American Journal of Human Genetics

Chi-Hyun Park, Youngji Moon, Chung Min Shin, Jin Ho Chung

Volume 25, Issue 21, Pages (November 2015)

Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome Fuxi Zhu, Fengsong Wang, Xiaoyu Yang, Jingjing Zhang, Huan Wu, Zhou.

The Actin-Bundling Protein Palladin Is an Akt1-Specific Substrate that Regulates Breast Cancer Cell Migration Y. Rebecca Chin, Alex Toker Molecular.

KRAS-MEK Signaling Controls Ago2 Sorting into Exosomes

Involvement of PI3K activation in TCR/CD3-dependent HIF-1α protein expression. Involvement of PI3K activation in TCR/CD3-dependent HIF-1α protein expression.

Loss of PTEN Expression by Dermal Fibroblasts Causes Skin Fibrosis

Hydroxychloroquine Modulates Metabolic Activity and Proliferation and Induces Autophagic Cell Death of Human Dermal Fibroblasts Bettina Ramser, Agatha.

J. Fielding Hejtmancik, Xiaodong Jiao, Anren Li, Yuri V

p38 MAPK activation is required for phosphorylation of Akt at Ser473.

X-Linked Dominant Scapuloperoneal Myopathy Is Due to a Mutation in the Gene Encoding Four-and-a-Half-LIM Protein 1 Catarina M. Quinzii, Tuan H. Vu, K.

Volume 17, Issue 12, Pages (December 2016)

Nan-Hyung Kim, Ai-Young Lee Journal of Investigative Dermatology

Yvonne Ng, Georg Ramm, Jamie A. Lopez, David E. James Cell Metabolism

All-Trans Retinoic Acid Antagonizes UV-Induced VEGF Production and Angiogenesis via the Inhibition of ERK Activation in Human Skin Keratinocytes Mi-Sun.

Expression of Matrix Metalloproteinase-13 Is Controlled by IL-13 via PI3K/Akt3 and PKC-δ in Normal Human Dermal Fibroblasts Chikako Moriya, Masatoshi.

Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas Qilin Zhang, Cheng Peng,

Mutations in NEXN, a Z-Disc Gene, Are Associated with Hypertrophic Cardiomyopathy Hu Wang, Zhaohui Li, Jizheng Wang, Kai Sun, Qiqiong Cui, Lei Song, Yubao.

Heterozygous Mutations in MAP3K7, Encoding TGF-β-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome Carine Le Goff, Curtis Rogers, Wilfried.

Hannah R. Elliott, David C. Samuels, James A. Eden, Caroline L

Zuoheng Wang, Mary Sara McPeek The American Journal of Human Genetics

PtdIns(3,4,5)P3 Regulates Spindle Orientation in Adherent Cells

Presentation transcript:

Germline PIK3CA and AKT1 Mutations in Cowden and Cowden-like Syndromes Mohammed S. Orloff, Xin He, Charissa Peterson, Fusong Chen, Jin-Lian Chen, Jessica L. Mester, Charis Eng The American Journal of Human Genetics Volume 92, Issue 1, Pages 76-80 (January 2013) DOI: 10.1016/j.ajhg.2012.10.021 Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 1 Spectrum of Germline PIK3CA Mutations in CS/CSL Individuals without PTEN Germline Mutations A display of amino acid changes that result from different germline PIK3CA mutations in CS/CSL individuals (blue arrows) relative to PIK3CA functional domains. The American Journal of Human Genetics 2013 92, 76-80DOI: (10.1016/j.ajhg.2012.10.021) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 2 AKT1 and PIK3CA Mutations Result in Upregulation of Phosphorylated P-Thr308-AKT1 (A) Western analysis of peripheral blood protein lysates from CS/CSL individuals with germline AKT1 and PIK3CA mutations. Mutation-positive individuals showed modest increase in p110α levels and marked increased levels of P-Thr308-AKT1 (arrow) but no detectable difference in P-Ser473-AKT1 and total (T)-AKT1 protein levels compared to controls. (B) Densitometric analysis of specific signals using Image J software. Signals were normalized to actin. A value of 100% was arbitrarily assigned to the ratio obtained in the controls (n = 4) and the relative ratio was made in the individuals with mutations (n = 8). Two-tailed Student’s t test was utilized. N.S., not significant. The American Journal of Human Genetics 2013 92, 76-80DOI: (10.1016/j.ajhg.2012.10.021) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 3 Increased PIP3 Levels in Lymphoblastoid Cell Lines (LCLs) Derived from PIK3CA Mutation-Positive Individuals (A) Indirect immunofluorescence staining of PIP3 (red) and DAPI (blue) in LCLs derived from an unaffected control (WT) and two CS individuals with PIK3CA germline mutations. (B) LCLs isolated from a CS individual harboring a PTEN germline mutation (p.Arg335∗) that were either treated or not treated with the PI3K inhibitor, Wortmannin (100 nM for 30 min), serve as positive control (left) and negative control (right) for PIP3 levels, respectively. The American Journal of Human Genetics 2013 92, 76-80DOI: (10.1016/j.ajhg.2012.10.021) Copyright © 2013 The American Society of Human Genetics Terms and Conditions