Eitan Friedman

Eitan Friedman
CUNY Graduate Center | CUNY · physiology, pharmacology & neuroscience

Ph.D.

About

278
Publications
11,147
Reads
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11,195
Citations
Additional affiliations
January 2001 - present
CUNY Graduate Center
Position
  • Medical professor
January 2001 - present
City College of New York
Position
  • medical professor and chair

Publications

Publications (278)
Article
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L-Dopa induced dyskinesia (LID) is a debilitating side effect of dopamine replacement therapy for Parkinson's Disease. The mechanistic underpinnings of LID remain obscure. Here we report that diminished sonic hedgehog (Shh) signaling in the basal ganglia caused by the degeneration of midbrain dopamine neurons facilitates the formation and expressio...
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The dopamine D5 receptor (D5R) is a Gαs-coupled dopamine receptor belonging to the dopamine D1-like receptor family. Together with the dopamine D2 receptor it is highly expressed in striatal cholinergic interneurons and therefore is poised to be a positive regulator of cholinergic activity in response to L-DOPA in the dopamine-depleted parkinsonian...
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The serotonin 4 receptor, 5-HT4R, represents one of seven different serotonin receptor families and is implicated in a variety of physiological functions and their pathophysiological variants, such as mood and depression or anxiety, food intake and obesity or anorexia, or memory and memory loss in Alzheimer’s disease. Its central nervous system exp...
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The serotonergic neurotransmitter system has been widely implicated in the pathophysiology of mood-related disorders such as anxiety and major depressive disorder (MDD). The onset of therapeutic efficacy of traditional antidepressants is delayed by several weeks. The 5-HT4 receptor has emerged as a new therapeutic target since agonists of this rece...
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We have previously shown that casein kinase 2 (CK2) negatively regulates dopamine D1 and adenosine A2A receptor signaling in the striatum. Ablation of CK2 in D1 receptor-positive striatal neurons caused enhanced locomotion and exploration at baseline, whereas CK2 ablation in D2 receptor-positive neurons caused increased locomotion after treatment w...
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Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical mod...
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Prenatal cocaine exposure causes profound changes in neurobehavior as well as synaptic function and structure with compromised glutamatergic transmission. Since synaptic health and glutamatergic activity are tightly regulated by brain-derived neurotrophic factor (BDNF) signaling through its cognate tyrosine receptor kinase B (TrkB), we hypothesized...
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Cocaine addiction has been associated with changes in synaptic plasticity, mediated in part by neurotrophin cascades. Given sex differences in cocaine addiction, we wanted to assess whether estradiol alters signaling of the brain-derived neurotrophic factor (BDNF), through interaction with its cognate receptor, tyrosine kinase B (Trk B), after repe...
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BACKGROUND: In a combined animal and human study, we have previously found that a 5-day treatment that enhances cortical plasticity also facilitates brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling and increases activated TrkB and N-methyl-d-aspartate receptor (NMDAR) association in both the cortex and the periph...
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Application of orthodox sigma-1 receptor agonists as anti-seizure drugs is dampened for the uncertainty in efficacy and potential adverse effects. In this study, we investigated the anti-seizure effects of the novel and potent allosteric modulator of the sigma-1 receptor SKF83959 and its derivative SOMCL-668 (3-methyl-phenyl-2,3,4,5-tetrahydro-1H-b...
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As an endogenous neuromodulator in the CNS, Taurine interacts with TAG (6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide)-sensitive and TAG-insensitive receptors. Taurine activates the former by opening a Cl⁻ channel and the latter by inhibiting the glutamate NMDA receptor. We sought to resolve the site of taurine’s interaction with the...
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Background Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of P...
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Cocaine exposure during gestation causes protracted neurobehavioral changes consistent with a compromised glutamatergic system. Although cocaine profoundly disrupts glutamatergic neurotransmission and in utero cocaine exposure negatively affects metabotropic glutamate receptor-type 1 (mGluR1) activity, the effect of prenatal cocaine exposure on mGl...
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Taurine is an endogenous brain substance with robust neuromodulatory and possible neuroprotective properties. Though other mechanisms of action have been reported, its interaction with the NMDA (N-Methyl-D-aspartic acid) receptor is undocumented. We investigated taurine's interaction with the NMDA receptor using electrophysiological and receptor bi...
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Taurine, an endogenous amino sulfonic acid, exhibits numerous neuropsychopharmacological activities. Previous studies in our laboratory have shown that it is an effective anti-cataleptic and neuro-protective agent. Current investigations show that acute or chronic administration of psychotropic drug cocaine may increase extracellular release of end...
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Taurine has neuroprotective capabilities against glutamate-induced excitotoxicity through several identified mechanisms including opening of the Cl(-)channel associated with GABA(A)and glycine receptors, or a distinct Cl(-)channel. No existing work has however shown a direct interaction of taurine with the glutamate NMDA receptor. Here we demonstra...
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Prenatal cocaine exposure causes sustained phosphorylation of the synaptic anchoring protein, glutamate receptor interacting protein (GRIP1/2), preventing synaptic targeting of the GluR2/3-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs; J. Neurosci. 29: 6308-6319, 2009). Because overexpression o...
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Cocaine use during pregnancy induces profound neural and behavioral deficits in both mother and offspring. The present study was designed to compare the effects of cocaine exposure on spine density of postpartum and virgin female rat brains. Timed, pregnant, primiparous rats were injected with either cocaine (30 mg/kg) or saline, once daily, from g...
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Repetitive transcranial magnetic stimulation (rTMS) induces neuronal long-term potentiation or depression. Although brain-derived neurotrophic factor (BDNF) and its cognate tyrosine receptor kinase B (TrkB) contribute to the effects of rTMS, their precise role and underlying mechanism remain poorly understood. Here we show that daily 5 Hz rTMS for...
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Cocaine exposure during pregnancy can impact brain development and have long-term behavioral consequences. The present study examined the lasting consequences of prenatal cocaine (PN-COC) exposure on the performance of cognitive tasks and dendritic spine density in adult male and female rats. From gestational day 8 to 20, dams were treated daily wi...
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It has been postulated that brain inflammatory processes associated with autoimmune diseases may be causative factors in emotional disorders. Accordingly, we examined emotional behaviors in autoimmune-prone cytokine B-cell-activating factor (BAFF) transgenic mice, a model of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome...
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Prenatal cocaine exposure produces sustained neurobehavioral and brain synaptic changes closely resembling those of animals with defective AMPA receptors (AMPARs). We hypothesized that prenatal cocaine exposure attenuates AMPAR signaling by interfering with AMPAR synaptic targeting. AMPAR function is governed by receptor cycling on and off the syna...
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The present study aims to define the role of postsynaptic density (PSD)-95 in the regulation of dopamine (DA) receptor function. We found that PSD-95 physically associates with either D(1) or D(2) DA receptors in co-transfected HEK-293 cells. Stimulation of DA receptors altered the association between D(1) receptor and PSD-95 in a time-dependent ma...
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Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate...
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Alterations in dendritic spine density following prenatal cocaine exposure were examined in the present study. Timed pregnant rats were injected daily with 30 mg/kg cocaine or saline during gestation. At postnatal day 21, male and female animals were separated and spine density was assessed following Golgi impregnation. In prenatal cocaine-exposed...
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Cocaine inhibits high-affinity neurotransmitter uptake at the presynaptic nerve terminals to increase synaptic levels of dopamine, norepinephrine and serotonin^1^. This increase of synaptic dopamine may cause neurotoxicity^2,3^. At least two different mechanisms have been proposed for the development of dopamine-related neurotoxicity: 1) dopamine p...
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The tetrahydroprotoberberines (THPBs) are compounds isolated from Chinese herbs that possess a unique pharmacological profile as D2 dopamine receptor antagonists and D1 receptor agonists. l-Tetrahydropalmatine (l-THP) and l-stepholidine (SPD), members of the THPB family, were shown to have potential clinical use in the treatment of pain. However, t...
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The aim of this study was to determine whether neocortical long-term potentiation (LTP) is deficient in patients with Alzheimer's disease (AD) and in amyloid precursor protein (APP)/presenilin-1 (PS1) mice, an AD animal model. We then ascertained whether this deficit might be paralleled by functional abnormalities of N-methyl-D-aspartate (NMDAR) gl...
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Females have been demonstrated repeatedly to be more sensitive to cocaine. The role of the frontal cortex (FCX) in mediating behavioral sensitization and the underlying signaling pathways are unclear. The study was designed to characterize the role of FCX calcium/calmodulin-dependent protein kinase II (CaMKII) activity in the behavioral supersensit...
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Abstract— A series of serotonin and phenethylamine analogs were tested for their ability to differentially inhibit type A or B monoamine oxidase (EC 1.4.3.4) in rat hypothalamus. The most specific and potent effects were shown by several tetrahydro-β-carbolines which competitively inhibited the oxidative deamination of serotonin at micromolar conce...
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: The effect of the Red Sea flatfish toxin pardaxin was examined on K+-evoked and on basal release of either [3H]norepinephrine or [3H]5-hydroxytryptamine from preloaded rat cortical slices. The K+-induced release of the neurotransmitters was stimulated in a dose-related manner at concentrations ranging from 0.5 to 4 μg/ml. Basal release of the two...
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Dysregulated protein kinase C (PKC) distribution and activation, and abnormal receptor-G protein coupling, have been implicated in the pathophysiology of bipolar affective disorder (BD). The therapeutic effectiveness of lithium has also been correlated with its ability to reduce PKC activation and G protein-mediated signaling. We examine the cellul...
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SKF83959, previously described as an antagonist of the D1 dopamine receptor, has been shown to be a potent anti-parkinsonian agent. However, its mechanism of action is unknown. The present communication was designed to study the mechanism by which SKF83959 exerts its pharmacological effects. SKF83959 induced contralateral rotations in the unilatera...
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Nuclear receptors are transcription factors that usually interact, in a ligand-dependent manner, with specific DNA sequences located within promoters of target genes. The nuclear receptors can also be controlled in a ligand-independent manner via the action of membrane receptors and cellular signaling pathways. 5-Tetradecyloxy-2-furancarboxylic aci...
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The authors examined the feasibility of using olfactory receptor neurons from living patients to test whether calcium signaling is altered in a neuronal cell population in bipolar disorder. Ratiometric fluorescence photomicroscopy was used to assess basal and stimulus-induced changes in intracellular calcium levels in biopsy-derived olfactory recep...
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Opiates produce analgesia by activating mu opioid receptor-linked inhibitory G protein signaling cascades and related ion channel interactions that suppress cellular activities by hyperpolarization. After chronic opiate exposure, an excitatory effect emerges contributing to analgesic tolerance and opioid-induced hyperalgesia. Ultra-low-dose opioid...
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A brain dopamine receptor that modulates phosphatidylinositol (PI) metabolism via the activation of phospholipase Cbeta (PLCbeta) has been described previously. The present study aims to define the downstream signaling cascade initiated by the PI-linked dopamine receptor. Incubation of rat brain frontal cortical slices with 6-chloro-7,8-dihydroxy-3...
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Prenatal cocaine exposure in rabbits induces cerebrocortical structural abnormalities. Glycogen synthase kinase-3beta (GSK3beta) plays an important role in neuronal development and survival. This study was designed to examine the effect of prenatal cocaine on brain GSK3beta. Rabbits exposed in utero to cocaine and assessed on postnatal day 20 had i...
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Previously a distinct D1-like dopamine receptor (DAR) that selectively couples to phospholipase C/phosphatidylinositol (PLC/PI) was proposed. However, lack of a selective agonist has limited efforts aimed at characterizing this receptor. We characterized the in vitro and in vivo effects of SKF83959 in regulating PI metabolism. SKF83959 stimulates (...
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Previous work demonstrated that stimulation of D(2) dopamine receptors (D(2)DRs) in the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat enhanced striatal extracellular signal-regulated kinase (ERK) activity ipsilateral to the lesion. The present work was designed to explore the mechanism underlying the activation of ERK in the denervated stria...
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Chronic interruption of the nigrostriatal dopaminergic pathway leads to sensitized dopaminergic responses in striatum. We attempted to explore the mechanism(s) underlying this dopaminergic supersensitivity by assessing dopamine receptor signaling and receptor-G protein coupling in unilateral 6-hydroxydopamine-lesioned rats. Dopamine-stimulated aden...
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: The effect of dopamine (DA) receptor stimulation on the distribution of γ protein kinase C (γPKC) in hippocampal slices was assessed. Nanomolar concentrations of DA decreased cytosolic γPKC (56%) without altering membrane γPKC levels, resulting in decreased total γPKC immunoreactivity. The maximal decrease in cytosolic γPKC occurred at 20 min of...
Article
Lithium has been shown to regulate multiple intracellular signaling pathways by affecting various protein kinases. However, the counterpart of protein kinases, i.e., protein phosphatases may play an important role in lithium-regulated cellular signaling and functions. The present work was designed to test the effect of lithium on protein phosphatas...
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Abstract Rationale. Lithium has been shown to regulate multiple intracellular signaling pathways by affecting various protein kinases. However, the counterpart of protein kinases, i.e., protein phosphatases may play an important role in lithium-regulated cellular signaling and functions. Objectives. The present work was designed to test the effec...
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Previous work has demonstrated that in utero cocaine exposure induces an uncoupling of brain D(1A) dopamine receptors (D(1A)DARs) from G(s)-protein. The present work is an attempt to define the mechanism underlying the uncoupling. We detected a significant elevation of phosphoserine in frontal cortical D(1A)DARs of rabbits that were exposed prenata...
Article
Previous results have suggested that the Ras signaling pathway is involved in learning and memory. Ras is activated by nucleotide exchange factors, such as the calmodulin-activated guanine-nucleotide releasing factor 1 (Ras-GRF1). To test whether Ras-GRF1 is required for learning and memory, we inactivated the Ras-GRF1 gene in mice. These mutants p...
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Lithium, an effective psychotropic agent, affects membrane phospholipid metabolism, interferes with phosphoinositide signal transduction, and antagonizes the biological activity of calcium, all major factors of protein kinase C (PKC) activation. Consequently, lithium may interfere with cellular functions requiring PKC. Supporting this hypothesis, l...
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The present study was designed to investigate the role of D(4) dopamine receptors in regulating the Akt/nuclear factor-kappa B (NF-kappa B) and extracellular signal-regulated kinase (ERK) signaling pathways. The D(4) dopamine receptor agonist PD168077 induced time- and dose-dependent activation of Akt and ERK in D(4)MN9D cells that stably express D...
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Background: Membrane protein kinase C (PKC) activity is increased in frontal cortex of subjects with bipolar affective disorder, and lithium was demonstrated to inhibit PKC translocation to membranes. Protein kinase C is anchored to the membrane via the receptor for activated C kinase-1 (RACK1), suggesting that interactions between these proteins...
Article
Previous studies have revealed that activation of rat striatal D(1) dopamine receptors stimulates both adenylyl cyclase and phospholipase C via G(s) and G(q), respectively. The differential distribution of these systems in brain supports the existence of distinct receptor systems. The present communication extends the study by examining other brain...
Article
This study examined the role of the mitogen-activated protein kinase (MAPK) family during acquisition of the rabbit's classically conditioned eye-blink response. Eye-blink conditioning produced a significant, bilateral activation of both extracellular signal-regulated protein kinases (ERKs) and p38 MAPK in the anterior cerebellar vermis. There was...
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To determine the effects of ischemia-reperfusion (I/R) on alpha(1)-adrenergic-receptor (alpha(1)-AR) functions, alpha(1)-AR-mediated contraction, inositol phosphate (IP) accumulation, and alpha(1)-AR-G protein coupling were examined in the tail arteries of anesthetized rats after 60 min of ischemia and 60 min of reperfusion. The contractile respons...
Article
Previous studies have revealed that activation of rat striatal D1 dopamine receptors stimulates both adenylyl cyclase and phospholipase C via Gs and Gq, respectively. The differential distribution of these systems in brain supports the existence of distinct receptor systems. The present communication extends the study by examining other brain regio...
Article
The effects of in utero cocaine exposure on cocaine-induced genomic and functional responses in postnatal life were examined. Pregnant Dutch Belted rabbits were injected intravenously, twice daily, with cocaine hydrochloride (4 mg/kg) or saline from day 8 through day 29 of pregnancy. Prenatally exposed kits were challenged with cocaine on postnatal...
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Earlier studies of human infants and studies employing animal models had indicated that prenatal exposure to cocaine produced developmental changes in the behavior of the offspring. The present paper reports on the results obtained in a rabbit model of in utero exposure to cocaine using intravenous injections (4 mg/kg, twice daily) that mimic the p...
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This study investigated the effects of advancing age and long-term aerobic fitness on lymphocyte protein kinase C (PKC) activity and translocation. Lymphocytes were obtained from young (20–36 years old) and older (61–78 years old) healthy men who were either aerobically conditioned or deconditioned. Both baseline PKC activity and the response of th...
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The purpose of this study was to determine whether the protective effects of adenosine on myocardial ischemia-reperfusion injury are altered with age, and if so, to clarify the mechanisms that underlie this change related to nitric oxide (NO) derived from the vascular endothelium. Isolated perfused rat hearts were exposed to 30 min of ischemia and...
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Monoamines modulate neuronal differentiation, and alteration of monoamine neurotransmission during development produces specific changes in neuronal structure, function, and pattern formation. We have previously observed that prenatal exposure to cocaine in a clinically relevant animal model produces increased length of pyramidal neuron dendrites i...
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This study examines the effects of adrenergic ligands, cholera toxin, forskolin, and varying levels of β2 adrenergic receptors (β2AR) on the cellular distribution of Gsα subunits in CHO cells. Localization of Gsα was evaluated by confocal microscopy and β2AR-mediated signalling was assessed by adenylyl cyclase (AC) activity. In cells expressing 0.2...
Article
Evidence indicates that mitogen-activated protein kinase (MAPK) pathways play a crucial role in the neurobiology of the nervous system. In the present study, dopamine receptor-mediated regulation of extracellular signal-regulated kinases (ERKs) was examined in rats in which the nigrostriatal dopaminergic pathway was unilaterally lesioned by 6-hydro...
Article
Full-text available
Mitogen-activated protein kinases (MAPKs) play important roles in cell proliferation, differentiation, and apoptosis. Important functional roles for MAPKs in postmitotic cells have recently been suggested. In the present study, we investigated the effect of aging on the brain ERK (extracellular signal-regulated kinase) and p38 MAPK signaling pathwa...