共 58 条
Neuronal NF1/RAS regulation of cyclic AMP requires atypical PKC activation
被引:61
作者:

Anastasaki, Corina
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

Gutmann, David H.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
机构:
[1] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
关键词:
PROTEIN-KINASE-C;
PLURIPOTENT STEM-CELLS;
NEUROFIBROMATOSIS TYPE-1;
ADENYLYL-CYCLASE;
RECEPTOR KINASE;
MOUSE MODEL;
MEK INHIBITION;
IN-VITRO;
RAS;
DROSOPHILA;
D O I:
10.1093/hmg/ddu389
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder in which affected individuals are prone to learning, attention and behavioral problems. Previous studies in mice and flies have yielded conflicting results regarding the specific effector pathways responsible for NF1 protein (neurofibromin) regulation of neuronal function, with both cyclic AMP (cAMP)- and RAS-dependent mechanisms described. Herein, we leverage a combination of induced pluripotent stem cell-derived NF1 patient neural progenitor cells and Nf1 genetically engineered mice to establish, for the first time, that neurofibromin regulation of cAMP requires RAS activation in human and mouse neurons. However, instead of involving RAS-mediated MEK/AKT signaling, RAS regulation of cAMP homeostasis operates through the activation of atypical protein kinase C zeta, leading to GRK2-driven G alpha(s) inactivation. These findings reveal a novel mechanism by which RAS can regulate cAMP levels in the mammalian brain.
引用
收藏
页码:6712 / 6721
页数:10
相关论文
共 58 条
[1]
G protein-coupled receptor kinase 2 (GRK2):: mechanisms of regulation and physiological functions
[J].
Aragay, AM
;
Ruiz-Gómez, A
;
Penela, P
;
Sarnago, S
;
Elorza, A
;
Jiménez-Sainz, MC
;
Mayor, F
.
FEBS LETTERS,
1998, 430 (1-2)
:37-40

Aragay, AM
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain

Ruiz-Gómez, A
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain

Penela, P
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain

Sarnago, S
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain

Elorza, A
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain

Jiménez-Sainz, MC
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain

Mayor, F
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain
[2]
THE NF1 LOCUS ENCODES A PROTEIN FUNCTIONALLY RELATED TO MAMMALIAN GAP AND YEAST IRA PROTEINS
[J].
BALLESTER, R
;
MARCHUK, D
;
BOGUSKI, M
;
SAULINO, A
;
LETCHER, R
;
WIGLER, M
;
COLLINS, F
.
CELL,
1990, 63 (04)
:851-859

BALLESTER, R
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109

MARCHUK, D
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109

BOGUSKI, M
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109

SAULINO, A
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109

LETCHER, R
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109

WIGLER, M
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109

COLLINS, F
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109
[3]
ABERRANT REGULATION OF RAS PROTEINS IN MALIGNANT-TUMOR CELLS FROM TYPE-1 NEUROFIBROMATOSIS PATIENTS
[J].
BASU, TN
;
GUTMANN, DH
;
FLETCHER, JA
;
GLOVER, TW
;
COLLINS, FS
;
DOWNWARD, J
.
NATURE,
1992, 356 (6371)
:713-715

BASU, TN
论文数: 0 引用数: 0
h-index: 0
机构: IMPERIAL CANC RES FUND,SIGNAL TRANSDUCT LAB,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND

GUTMANN, DH
论文数: 0 引用数: 0
h-index: 0
机构: IMPERIAL CANC RES FUND,SIGNAL TRANSDUCT LAB,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND

FLETCHER, JA
论文数: 0 引用数: 0
h-index: 0
机构: IMPERIAL CANC RES FUND,SIGNAL TRANSDUCT LAB,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND

GLOVER, TW
论文数: 0 引用数: 0
h-index: 0
机构: IMPERIAL CANC RES FUND,SIGNAL TRANSDUCT LAB,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND

COLLINS, FS
论文数: 0 引用数: 0
h-index: 0
机构: IMPERIAL CANC RES FUND,SIGNAL TRANSDUCT LAB,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND

DOWNWARD, J
论文数: 0 引用数: 0
h-index: 0
机构: IMPERIAL CANC RES FUND,SIGNAL TRANSDUCT LAB,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND
[4]
TARGETED DISRUPTION OF THE NEUROFIBROMATOSIS TYPE-1 GENE LEADS TO DEVELOPMENTAL ABNORMALITIES IN HEART AND VARIOUS NEURAL CREST-DERIVED TISSUES
[J].
BRANNAN, CI
;
PERKINS, AS
;
VOGEL, KS
;
RATNER, N
;
NORDLUND, ML
;
REID, SW
;
BUCHBERG, AM
;
JENKINS, NA
;
PARADA, LF
;
COPELAND, NG
.
GENES & DEVELOPMENT,
1994, 8 (09)
:1019-1029

BRANNAN, CI
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437

PERKINS, AS
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437

VOGEL, KS
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437

论文数: 引用数:
h-index:
机构:

NORDLUND, ML
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437

REID, SW
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437

BUCHBERG, AM
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437

JENKINS, NA
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437

PARADA, LF
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437

COPELAND, NG
论文数: 0 引用数: 0
h-index: 0
机构: YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437
[5]
Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder
[J].
Braun, BS
;
Tuveson, DA
;
Kong, N
;
Le, DT
;
Kogan, SC
;
Rozmus, J
;
Le Beau, MM
;
Jacks, TE
;
Shannon, KM
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2004, 101 (02)
:597-602

Braun, BS
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

Tuveson, DA
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

Kong, N
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

Le, DT
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

Kogan, SC
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

Rozmus, J
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

Le Beau, MM
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

Jacks, TE
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

Shannon, KM
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
[6]
Neurofibromatosis-1 heterozygosity impairs CNS neuronal morphology in a cAMP/PKA/ROCK-dependent manner
[J].
Brown, Jacquelyn A.
;
Diggs-Andrews, Kelly A.
;
Gianino, Scott M.
;
Gutmann, David H.
.
MOLECULAR AND CELLULAR NEUROSCIENCE,
2012, 49 (01)
:13-22

Brown, Jacquelyn A.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

Diggs-Andrews, Kelly A.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

Gianino, Scott M.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

Gutmann, David H.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[7]
Defective cAMP Generation Underlies the Sensitivity of CNS Neurons to Neurofibromatosis-1 Heterozygosity
[J].
Brown, Jacquelyn A.
;
Gianino, Scott M.
;
Gutmann, David H.
.
JOURNAL OF NEUROSCIENCE,
2010, 30 (16)
:5579-5589

Brown, Jacquelyn A.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

Gianino, Scott M.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

Gutmann, David H.
论文数: 0 引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[8]
A Distinct Set of Drosophila Brain Neurons Required for Neurofibromatosis Type 1-Dependent Learning and Memory
[J].
Buchanan, Monica E.
;
Davis, Ronald L.
.
JOURNAL OF NEUROSCIENCE,
2010, 30 (30)
:10135-10143

Buchanan, Monica E.
论文数: 0 引用数: 0
h-index: 0
机构:
Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

Davis, Ronald L.
论文数: 0 引用数: 0
h-index: 0
机构:
Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[9]
Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1
[J].
Costa, RM
;
Federov, NB
;
Kogan, JH
;
Murphy, GG
;
Stern, J
;
Ohno, M
;
Kucherlapati, R
;
Jacks, T
;
Silva, AJ
.
NATURE,
2002, 415 (6871)
:526-530

Costa, RM
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA

Federov, NB
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA

Kogan, JH
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA

Murphy, GG
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA

Stern, J
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA

Ohno, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA

Kucherlapati, R
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA

Jacks, T
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA

Silva, AJ
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA Univ Calif Los Angeles, BRI, Dept Neurobiol, Los Angeles, CA 90095 USA
[10]
RETRACTED: G Protein-coupled Receptor Kinase-2 Is a Novel Regulator of Collagen Synthesis in Adult Human Cardiac Fibroblasts (Retracted Article)
[J].
D'Souza, Karen M.
;
Malhotra, Ricky
;
Philip, Jennifer L.
;
Staron, Michelle L.
;
Theccanat, Tiju
;
Jeevanandam, Valluvan
;
Akhter, Shahab A.
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2011, 286 (17)
:15507-15516

D'Souza, Karen M.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA

Malhotra, Ricky
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA

Philip, Jennifer L.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA

Staron, Michelle L.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA

Theccanat, Tiju
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA

Jeevanandam, Valluvan
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA

Akhter, Shahab A.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA Univ Chicago, Med Ctr, Dept Surg, Sect Cardiac & Thorac Surg, Chicago, IL 60637 USA