Trk receptors: mediators of neurotrophin action

Patapoutian, Ardem; Reichardt, Louis F.

doi:10.1016/s0959-4388(00)00208-7

Cited by 973 publications

(784 citation statements)

References 79 publications

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“…PI3-kinase is the major regulator of neurotrophin-mediated survival in cortical, hippocampal, sensory, and motor neurons (Yao and Cooper, 1995;Skaper et al, 1998;Dolcet et al, 1999;Hetman et al, 1999;Liot et al, 2004), as well as glia (Rodgers and Theibert, 2002). One of the most important targets of PI 3-kinase is Akt (Vanhaesebroeck and Alessi, 2000;Patapoutian and Reichardt, 2001), which is activated after binding with the PI 3-kinase lipid product PI-3,4,5-P 3 or through phosphorylation by another target of PI 3-kinase, that is, PI-dependent kinase-1 (PDK-1) (Alessi et al, 1997). Akt, in turn, inhibits Forkhead transcription factors, responsible for inducing expression of death genes; phosphorylates and therefore inhibits glycogen synthase kinase-3b activity, involved in neuronal apoptosis (Patapoutian and Reichardt, 2001); induces expression of survival genes, such as Bcl-2 and Bcl-x L , by activating cyclicAMP response element binding protein and nuclear factor-kB (Downward, 2004); phosphorylates and deactivates proapoptotic Bad (Datta et al, 2000) and caspase-9 (Zhou et al, 2000); and blocks proapoptotic action of the p75 neurotrophin receptor ).…”

Section: Discussionmentioning

confidence: 99%

“…One of the most important targets of PI 3-kinase is Akt (Vanhaesebroeck and Alessi, 2000;Patapoutian and Reichardt, 2001), which is activated after binding with the PI 3-kinase lipid product PI-3,4,5-P 3 or through phosphorylation by another target of PI 3-kinase, that is, PI-dependent kinase-1 (PDK-1) (Alessi et al, 1997). Akt, in turn, inhibits Forkhead transcription factors, responsible for inducing expression of death genes; phosphorylates and therefore inhibits glycogen synthase kinase-3b activity, involved in neuronal apoptosis (Patapoutian and Reichardt, 2001); induces expression of survival genes, such as Bcl-2 and Bcl-x L , by activating cyclicAMP response element binding protein and nuclear factor-kB (Downward, 2004); phosphorylates and deactivates proapoptotic Bad (Datta et al, 2000) and caspase-9 (Zhou et al, 2000); and blocks proapoptotic action of the p75 neurotrophin receptor ). Interestingly, activation of PDK-1 leads to phosphorylation and activation of protein kinase C (PKC) family members (Chou et al, 1998;Le Good et al, 1998), and PI-3,4,5-P 3 in response to growth factor activation enhances phospholipase C (PLC)g activity (Falasca et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…PI-3,4,5-P 3 , formed in response to the phosphorylation of PI-4,5-P 2 , then recruits proteins that contain a pleckstrin homology (PH) domain to the plasma membrane. Along with the direct recruitment of PI 3-kinase, many Trks also recruit adapter proteins, such as Shc, Grb2, Gab-1, via phosphorylated tyrosine residues in the receptor Patapoutian and Reichardt, 2001). Some of these adapters bind the SH2 domains in the p85 regulatory subunit and recruit PI 3-kinase to the plasma membrane.…”

Section: Introductionmentioning

confidence: 99%

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Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Dwivedi

Rizavi

Teppen

et al. 2007

Neuropsychopharmacol

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Phosphoinositide 3 (PI 3)-kinase is one of the key signaling enzymes that participates in a myriad of physiological functions in brain and is utilized by neurotrophins to mediate neuronal plasticity, cell survival, and inhibition of apoptosis for several neuronal subtypes. Our recent demonstration that expression of neurotrophic factors and activation of the receptor tyrosine kinase B are significantly altered in postmortem brain of suicide subjects led us to examine whether suicide brain is associated with alterations in PI 3-kinase signaling. In prefrontal cortex (PFC), hippocampus, and cerebellum of suicide (n ¼ 28) and nonpsychiatric control (n ¼ 21) subjects we examined catalytic activation of PI 3-kinase, and mRNA and protein levels of regulatory (p85a, p85b) and catalytic (p110a, p110b) subunits of PI 3-kinase. It was observed that the catalytic activity of PI 3-kinase was significantly reduced in PFC and hippocampus of suicide subjects compared with nonpsychiatric control subjects. Competitive PCR analysis revealed significantly reduced mRNA expression of p85b and p110a and increased expression of p85a subunit isoforms in PFC and hippocampus of suicide subjects. Alterations in these catalytic and regulatory subunits were accompanied by changes in their respective protein levels. These changes were not present in cerebellum of suicide subjects. Also, these changes were present in all suicide subjects irrespective of psychiatric diagnosis. Our findings of reduced activation and altered expression of specific PI 3-kinase regulatory and catalytic subunit isoforms demonstrate abnormalities in this signaling pathway in postmortem brain of suicide subjects and suggest possible involvement of aberrant PI 3-kinase signaling in the pathogenic mechanisms of suicide.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Dwivedi

Rizavi

Teppen

et al. 2007

Neuropsychopharmacol

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“…However, recent findings point to the likelihood that also nuclear PI3K plays an essential role in promoting cell survival through nuclear PtdIns (3,4,5)P 3 and Akt. In PC12 cells, NGF treatment elicits powerful anti-apoptotic signaling cascades [Patapoutian and Reichardt, 2001]. In response to NGF, PI-PLCg1 translocates to the nucleus where it acts as a physiological guanine-nucleotide-exchange factor for PIKE-S [Ye et al, 2002].…”

Section: New Roles For Nuclear Pi3k Andmentioning

confidence: 99%

Nuclear inositol lipid metabolism: More than just second messenger generation?

Martelli

Follo

Evangelisti

et al. 2005

J of Cellular Biochemistry

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A distinct polyphosphoinositide cycle is present in the nucleus, and growing evidence suggests its importance in DNA replication, gene transcription, and apoptosis. Even though it was initially thought that nuclear inositol lipids would function as a source for second messengers, recent findings strongly indicate that lipids present in the nucleus also fulfil other roles. The scope of this review is to highlight the most intriguing advances made in the field over the last few years, such as the possibility that nuclear phosphatidylinositol (4,5) bisphosphate is involved in maintaining chromatin in a transcriptionally active conformation, the new emerging roles for intranuclear phosphatidylinositol (3,4,5) trisphosphate and phosphoinositide 3-kinase, and the evidence which suggests a tight relationship between a decreased level of nuclear phosphoinositide specific phospholipase C-b1 and the evolution of myelodisplastic syndrome into acute myeloid leukemia.

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“…Thus an elucidation of the cellular and molecular interactions that occur after neural crest migration yet before the completion of target innervation, is required because it is during this time period when all of neurogenesis and the onset of differentiation of discrete classes of sensory neurons occurs (Rifkin et al, 2000;Oakley and Karpinski, 2002;Guan and Condic, 2003). Several key regulatory molecules have been identified in sensory neural development, including neurotrophic factors and their receptors, transcription factors such as Neurogenin 1 and Neurogenin 2, ETS family members, and Notch-Delta and ␤-catenin signaling pathways (Ma et al, 1999;Lin et al, 1998;Arber et al, 2000;Wakamatsu et al, 2000;Patapoutian and Reichardt, 2001;Hari et al, 2002). Though these molecules and pathways play important roles during DRG development, they alone cannot fully account for the developmental processes underlying the genesis and differentiation of discrete cell types.…”

Section: Introductionmentioning

confidence: 99%

Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia

Nelson

Sadhu

Kasemeier

et al. 2004

Developmental Dynamics

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The dorsal root ganglia (DRG) derive from a population of migrating neural crest cells that coalesce laterally to the neural tube. As the DRG matures, discrete cell types emerge from a pool of differentiating progenitor cells. To identify genes that regulate sensory genesis and differentiation, we have designed screens to identify members from families of known regulatory molecules such as receptor tyrosine kinases, and generated full-length and subtractive cDNA libraries between immature and mature DRG for identifying novel genes not previously implicated in DRG development. Several genes were identified in these analyses that belong to important regulatory gene families. Quantitative PCR confirmed differential expression of candidate cDNAs identified from the subtraction/differential screening. In situ hybridization further validated dynamic expression of several cDNAs identified in our screens. Our results demonstrate the utility of combining specific and general screening approaches for isolating key regulatory genes involved in the genesis and differentiation of discrete cell types and tissues within the classic embryonic chick model system. Developmental Dynamics 229:618 -629, 2004.

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Trk receptors: mediators of neurotrophin action

Cited by 973 publications

References 79 publications

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Nuclear inositol lipid metabolism: More than just second messenger generation?

Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia

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