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PubMed1987

Release of atrial natriuretic polypeptide by graded right atrial distension in anesthetized dogs.

In order to verify the contribution of right atrial pressure to atrial natriuretic polypeptides (ANP) release, we measured plasma levels of immunoreactive (ir)-ANP when graded rise of right atrial pressure was executed in anesthetized dogs. Increasing right atrial pressure (RAP) from 2.7 +/- 0.6 to 9.0 +/- 0.7 mmHg, plasma levels of ir-ANP in aorta tended to increase by 33% but not significantly (p greater than 0.05). However, when RAP was increased from 9.0 +/- 0.7 to 17.0 +/- 1.1 mmHg, ir-ANP levels in aorta were significantly (p less than 0.05) increased by 132% of control within 5 min from the start of RAP elevation. The RAP elevation produced a sustained increase in plasma levels of ir-ANP. There was a positive correlation between right atrial pressure and plasma levels of ir-ANP. The plasma levels of ir-ANP were similar between aorta and pulmonary artery. These results demonstrate that increasing atrial pressure is closely correlated with ANP release and ANP is not greatly metabolized by pulmonary circulation.

Animals↗

PubMed1996

Preoptic recess lesions reduce right atrial pressure responses to volume expansion.

Ablation of the periventricular tissue surrounding the anteroventral portion of the third cerebral ventricle (AV3V-X) abolishes natriuresis and diuresis during volume expansion. Although deficits in several efferent mechanisms have been identified, effects of AV3V-X on afferent input to the volume reflex have not been investigated. Therefore, these experiments measured right atrial pressure (RAP) in conscious AV3V-X and control-operated (CONT) rats before, during, and following acute (60 s) or continuous (60 min) infusion of isotonic saline, or vascular volume expansion with whole blood (15 min). Changes in RAP were significantly smaller in AV3V-X rats than CONT animals during acute isotonic saline infusion and during whole-blood expansion. Treatment with hexamethonium abolished the difference in RAP during acute volume infusion. However, there was no significant difference in RAP between groups during continuous isotonic saline expansion. These data suggest that AV3V-X reduces afferent input from cardiopulmonary stretch receptors during acute volume expansion, which may contribute to diminished natriuresis and diuresis observed in these animals.

Animals↗

PubMed1982

Potential biobehavioral mechanisms of recurrent abdominal pain in children.

To explain why otherwise healthy children experience recurrent episodes of abdominal pain (the recurrent abdominal pain syndrome, or RAP), it has been hypothesized that the child with RAP demonstrates: (1) a deficit in autonomic nervous system recovery to stress, and/or (2) an enhanced behavioral and subjective response to pain. To evaluate the validity of these assumptions, children with RAP (9-14 years) and hospital and healthy controls matched for age, sex, ethnicity and SES were exposed to a cold pressor stimulus (0 +/- 1 degree C). Autonomic (peripheral vasomotor and heart rate), somatic (forearm EMG), subjective (pain intensity and distress), and behavioral (facial expression) responses were recorded during baseline, stressor and recovery periods. At all 4 levels of observation, the cold pressor stimulus resulted in significant autonomic, somatic, subjective and behavioral arousal. However, no significant differential response across the 3 groups was noted for any measure and, in particular, no recovery deficit in autonomic arousal was demonstrated. These findings do not support the assumption of a differential response to an acute laboratory induced stress in children with RAP compared to control children.

Abdomen↗

PubMed2005

New micro vertical scissors for the surgical ablation of retinal angiomatous proliferation.

PURPOSE: To develop new micro vertical scissors for the ablation of retinal angiomatous proliferation (RAP) to minimize possible retinal damage. DESIGN: Interventional case report. METHODS: New micro vertical scissors were developed and used for the ablation of RAP vessels. RESULTS: The length of the inner side of the tip is 180 microm, which is approximately one seventh that of regular vertical scissors. The scissors handled easily and the RAP vessels were ablated with less retinal damage compared with that associated with use of standard vertical scissors. Postoperatively, intraretinal hemorrhage was reduced and hyperfluorescence seen on indocyanine green angiography resolved. CONCLUSIONS: The new micro vertical scissors developed for the ablation of RAP vessels can be used safely and effectively during this surgical procedure.

Aged↗

PubMed2005

Dipole localization using simulated intracerebral EEG.

OBJECTIVE: In the clinical interpretation of intracerebral EEGs, epileptic foci are commonly identified by visually analyzing the amplitude of the potentials. This is potentially misleading since electrodes record activity from several sources, but the nearest ones generate large amplitudes that can overpower distant sources. Our objective was to improve foci detection in intracerebral recordings by applying source localization methods. METHODS: Data were simulated by placing 3 sources in a semi-infinite medium near 3 intracerebral electrodes. Potentials were generated and contaminated with white and correlated noise. Two inverse problem algorithms, beamforming and RAP-MUSIC, were used to calculate equivalent dipoles. RESULTS: Simulations for each noise types showed that the two methods detected the source locations accurately, with RAP-MUSIC reporting lower orientation errors. With correlated noise, beamforming reconstructed original source waveforms poorly. A spatial resolution analysis was performed, in which beamforming adequately distinguished sources separated by 1.2 cm, whereas RAP-MUSIC separated sources as close as 0.4-0.6 cm. CONCLUSIONS: Both source localization methods proved useful in detecting the location of dipolar sources based on simulated intracerebral potentials. For all simulations, RAP-MUSIC was more accurate than beamforming. SIGNIFICANCE: It is possible to use source localization methods traditionally applied to scalp recordings for improving source detection from intracerebral recordings.

Algorithms↗

PubMed2004

Impaired gap detection in juvenile microgyric rats.

Previous research with adult animal models links the presence of cortical neuromigrational anomalies (i.e., microgyria similar to that found in brains of dyslexics) with rapid auditory processing (RAP) impairments. RAP impairments are in turn found in children with specific language impairment (SLI) and also in individuals with dyslexia. Gap detection, a simple measure of auditory temporal acuity, appears to be impaired in children with SLI but not in dyslexic adults, even though both groups exhibit impaired processing on more complex, rapid auditory tasks. In the current study, juvenile rats with bilateral microgyria, but not their adult counterparts, exhibited impaired detection of short duration silent gaps in white noise when compared to age-matched sham littermates. Results lend further support to: (1) an association between neuromigrational anomalies and RAP impairments; and (2) the validity of an animal model of RAP impairments associated with language disturbances in humans. Current results also support the view that auditory processing disturbances associated with cortical malformations may be evident early in development at a relatively "low" level (e.g., simple gap detection), but may require "higher-order" auditory discrimination tasks (e.g., tone sequences, phonemic discriminations) to be elicited later in life.

Acoustic Stimulation↗

PubMed2005

Methods for identifying extracellular ligands of RPTPs.

The transmembrane forms of the protein tyrosine phosphatases (PTPs) are evolutionarily conserved and have been implicated in diverse cellular and developmental functions. Due to their structure, these enzymes are known as "receptor-like" PTPs (RPTPs), yet most remain as orphan receptors with no proven ligands yet. The question of whether or not such ligands exist is critical, because RPTP regulation by extracellular cues could be central to their signal transduction mechanisms. Identification of ligands has therefore been an important goal in the field. However, even with powerful genetic and molecular techniques at our disposal, this goal has frequently been met with frustration. This review focuses on methods used in the search for such ligands and primarily on a commonly employed technique named RAP in situ. RAP in situ has been used with some success in recent years and relies on the ability of isolated extracellular domains of receptors to still recognise their cognate ligand partners in vitro. For this technique, fusion proteins are made between RPTP ectodomains and placental alkaline phosphatase and these fusion proteins are used to probe tissue sections, live cultured cells or whole tissues. The binding sites of the proteins are visualised by alkaline phosphatase histochemistry, directly pinpointing the location of potential ligands. RAP in situ has helped to identify ligands for PTPzeta/beta and PTPsigma, as well as locating several other putative ligand sites in tissues. We provide troubleshooting details for RAP in situ and describe some other complementary techniques that can be used.

Animals↗

PubMed1995

The Rehabilitation Activities Profile: a validation study of its use as a disability index with stroke patients.

OBJECTIVE: This study evaluates the criterion, content, and construct validity of the Rehabilitation Activities Profile (RAP) in patients with stroke. This instrument is constructed for screening, monitoring, and prognosis purposes to assist clinical rehabilitation. It consists of 21 activities, covering the domains communication, mobility, personal care, occupation, and relationships. Disabilities and perceived problems are assessed in parallel on two four-point severity scales. The disability sum scores of the first four RAP domains were used in the analyses presented in this article. DESIGN: An inception cohort of stroke patients was studied during 26 weeks. Patients that were still hospitalized on the 14th day after stroke were included. The functional assessments took place 2, 3, 4, 8, 12, and 26 weeks after stroke. SETTING: The patients were visited at the hospital, at home, nursing home, or rehabilitation center. PATIENTS: 125 patients were included in the study. After 26 weeks, 105 patients were still alive; 18 patients had died, and 2 patients were lost to follow-up. MAIN OUTCOME MEASURES: The RAP, Barthel Index (BI) and Frenchay Activities Index (FAI). RESULTS: The domain "mobility+personal care" correlated highly with the BI score (r: 0.87 to 0.90). The domain "occupation" correlated with the FAI score before the stroke and 26 weeks after stroke (r: 0.72, 0.73, respectively). The disability sum score of the domain "mobility+personal care" allowed a prediction of the living arrangement 26 weeks after stroke (receiver operator characteristic area surface: 0.90). The same domain showed significant differences (p < 0.05) in the 8-week disability sum score for most living arrangements. Exceptions were rehabilitation center versus intermediate care in a nursing home (p = 0.23) and acute care hospital versus chronic care in a nursing home (p = 0.45). Hypotheses on subgroup differences in mean scores in the domains "communication" and "mobility+personal care" could be confirmed (the discerned subgroups were: gender, having a partner, motor deficit of upper or lower extremity, urinary incontinence, higher cortical deficits, conjugate deviation of the eye, coma, hemianopsia). CONCLUSION: The disability sum scores of the RAP can be used as discriminative, evaluative, and predictive indexes.

Aged↗

PubMed1997

Evidence for differential roles of the Rho subfamily of GTP-binding proteins in glucose- and calcium-induced insulin secretion from pancreatic beta cells.

We utilized clostridial toxins (with known specificities for inhibition of GTPases) to ascertain the contribution of candidate GTPases in physiologic insulin secretion from beta cells. Exposure of normal rat islets or isolated beta (HIT-T15) cells to Clostridium difficile toxins A and B catalyzed the glucosylation (and thereby the inactivation) of Rac, Cdc42, and Rho endogenous to beta cells; concomitantly, either toxin reduced glucose- or potassium-induced insulin secretion from rat islets and HIT cells. Treatment of beta cells with Clostridium sordellii lethal toxin (LT; which modified only Ras, Rap, and Rac) also reduced glucose- or potassium-induced secretion. However, clostridial toxin C3-exoenzyme (which ADP-ribosylates and inactivates only Rho) was without any effect on either glucose- or potassium-induced insulin secretion. These data suggest that Cdc42, Rac, Ras, and/or Rap (but not Rho) may be needed for glucose- or potassium-mediated secretion. The effects of these toxins appear to be specific on stimulus-secretion coupling, since no difference in metabolic viability (assessed colorimetrically by quantitating the conversion of the tetrazolium salt into a formazan in a reduction reaction driven by nutrient metabolism) was demonstrable between control and toxin (A or LT)-treated beta cells. Toxin (A or LT) treatment also did not alter glucose- or potassium-mediated rises in cytosolic free calcium concentrations ([Ca2+]i), suggesting that these GTPases are involved in steps distal to elevations in [Ca2+]i. Recent findings indicate that the carboxyl methylation of Cdc42 is stimulated by only glucose, whereas that of Rap (Kowluru et al., J Clin Invest 98: 540-555, 1996) and Rac (present study) are regulated by glucose or potassium. Together, these findings provide direct evidence, for the first time, that the Rho subfamily of GTPases plays a key regulatory role(s) in insulin secretion, and they suggest that Cdc42 may be required for early steps in glucose stimulation of insulin release, whereas Rap and/or Rac may be required for a later step(s) in the stimulus-secretion coupling cascade (i.e. Ca2+-induced exocytosis of insulin).

ADP Ribose Transferases↗

PubMed1996

Laparoscopy for diagnosis and treatment of recurrent abdominal pain in children.

Extensive radiographic evaluation of children with recurrent abdominal pain (RAP) is rarely diagnostic or cost-effective. The authors sought to define the role of laparoscopy in the evaluation of children with RAP. Fifteen children underwent laparoscopy for RAP in a 2-year period. Their mean age was 12 years (range, 6 to 16 years), 13 (87%) were female, and the mean duration of symptoms was 11 months (range, 2 to 60 months). Thirty-eight imaging studies (excluding plain films) had been obtained before laparoscopy, including 19 abdominal sonograms, 9 upper gastrointestinal series, four abdominal computed tomography scans, 3 barium enemas, 2 isotope scans, and 1 magnetic resonance examination of the head. Only two (5%) of these studies provided an accurate diagnosis. Eleven of the 15 children (73%) had positive findings diagnosed and treated laparoscopically. These included eight appendiceal abnormalities (in six patients), three Meckel's diverticula, one inguinal hernia, one urachal cyst, one para-fallopian tube cyst, and one adhesion to an appendectomy stump. Eight of 11 (73%) children with positive findings had immediate resolution of symptoms after laparoscopic treatment. Three children with pathological findings at the time of laparoscopy had persistent symptoms, which resolved completely within 4 months of the laparoscopy. Laparoscopy is an accurate technique for the evaluation and treatment of children with RAP. Its early application could provide economic benefit by eliminating many low-yield imaging studies and minimizing lost time from school.

Abdominal Pain↗

PubMed1985

Depressive symptoms in children with recurrent abdominal pain and in their families.

Our purpose was to evaluate depression in children with recurrent abdominal pain and in their families. A self-report measure, the Children's Depression Inventory, and a psychiatric structured interview, the Child Assessment Schedule, were administered to 25 children with recurrent abdominal pain (RAP) as well as to 67 behaviorally disordered (BD) and 42 healthy children. Parents of all three groups completed the Beck Depression Inventory. On both measures, scores for RAP children were not significantly different from those of healthy children and were significantly lower than those of BD children. In contrast, the mothers of both the RAP group and the BD group had significantly higher depression scores than the mothers of healthy children. There were no group differences for fathers. The data suggest that although depression is not prevalent in children with RAP, depressive characteristics in the family may play a role in the origin of their abdominal pain.

Abdomen↗

PubMed2001

The significance of life-events as contributing factors in childhood recurrent abdominal pain in an urban community in Malaysia.

This study aimed to look at the link between childhood recurrent abdominal pain (RAP) and the presence of recent life-events in an urban community in Malaysia. School children aged from 9 to 15 years in the city of Petaling Jaya were randomly selected to fill in a questionnaire and to be interviewed. The prevalence of RAP among 1488 school children studied was 9.6% (95% confidence interval (CI), 8.18-11.25). Higher prevalences of RAP were found in children who had experienced the following life-events in the previous year: loss of a family member through death (P<.001), hospitalisation of a family member (P<.001), the child's own hospitalisation (P=.001), change of address (P<.001), change in occupation of an immediate family member (P<.001), failure in a major school examination (P<.001), bullying at school (P=.001). Following logistic regression analysis, five life-events remain significant: hospitalisation of a family member (P=.038), the child's own hospitalisation (P=.034), change in occupation of an immediate family member (P=.049), examination failure (P=.001) and bullying at school (P=.028). This study strongly suggests that recent stressful life-events are important risk-factors for RAP.

Abdominal Pain↗

PubMed2006

Purification of ARAP3 and characterization of GAP activities.

ARAP3 is a dual Arf and Rho GTPase activating protein (GAP) that was identified from pig leukocyte cytosol using a phosphatidylinositol-(3,4,5)-trisphosphate (PtdIns[3,4,5]P3) affinity matrix in a targeted proteomics study. ARAP3's domain structure includes five PH domains, an Arf GAP domain, three ankyrin repeats, a Rho GAP domain, and a Ras association domain. ARAP3 is a PtdIns(3,4,5)P3-dependent GAP for Arf6 both in vitro and in vivo. It acts as a Rap-GTP-activated RhoA GAP in vitro, and this activation depends on a direct interaction between ARAP3 and Rap-GTP; in vivo PtdIns(3,4,5)P3 seems to be required to allow ARAP3's activation as a RhoA GAP by Rap-GTP. Overexpression of ARAP3 in pig aortic endothelial (PAE) cells causes the PI3K-dependent loss of adhesion to the substratum and interferes with lamellipodium formation. This overexpression phenotype depends on ARAP3's intact abilities to bind PtdIns(3,4,5)P3, to interact with Rap-GTP, and to be a catalytically active RhoA and Arf6 GAP.

ADP-Ribosylation Factor 6↗

PubMed1998

Solution studies of the antitumor complex dichloro 1,2-propylendiaminetetraacetate ruthenium (III) and of its interactions with proteins.

A mixed complex of ruthenium (III) with 1,2-propylendiaminetetraacetate (PDTA) and chloride--RAP hereafter--has been found to exhibit favorable anticancer properties in vivo. To get some insight into the possible mechanism of action of this ruthenium (III) complex, its solution behavior and reactivity with proteins were investigated through absorption, circular dichroism and 1H NMR spectroscopies. Under physiological conditions RAP slowly looses the two coordinated chlorine atoms to produce a number of ruthenium (III) reactive species; a description of the distribution of these species on the dependence of pH has been obtained through 1H NMR studies of the hyperfine shifted signals. Remarkably, through the different solution conditions employed in this study, the ruthenium ion always remains in the 3+ oxidation state and the PDTA ligand is always bound to the metal. Upon reaction with albumin, apotransferrin or diferric transferrin, at a 1:1 ratio, RAP rapidly binds to these proteins to produce substantially equivalent and relatively stable adducts. This behavior is tentatively interpreted in terms of a tight interaction between RAP and surface residues of these proteins. The implications of these findings for the biological action of this novel ruthenium (III) compound are discussed.

Antineoplastic Agents↗

PubMed1982

Coronary perfusion pressure during experimental cardiopulmonary resuscitation.

Systemic blood flow during cardiopulmonary resuscitation may result from alterations in intrapleural pressure (IPP), with the heart serving only as a passive conduit. Chest compression with simultaneous lung inflation (C + SI) or with abdominal binding may also increase vascular pressures and cerebral flow. Our study was done to evaluate the effects of C + SI with and without abdominal binding on coronary perfusion pressure (CPP) during CPR. Micromanometric pressures were recorded in 7 dogs during ventricular fibrillation (VF) and CPR to evaluate CPP (aortic minus right atrial pressure). During chest compression alone, aortic (AoP) and right atrial (RAP) pressures did not differ significantly. During relaxation, AoP (15 +/- 4 mm Hg) was greater than RAP (3 +/- 2 mm Hg; P less than 0.001) and diastolic CPP averaged 12 +/- 4 mm Hg. C + SI significantly increased AoP, RAP, and IPP, but did not improve systolic or diastolic CPP. Tight abdominal binding during chest compression alone or during C + SI also increased AoP and RAP and caused a slight but insignificant decrease in diastolic CPP. Extravascular resistance to coronary flow during VP has been shown to average 28 mm Hg in the in vitro heart. Our study indicates that CPPs calculated during CPR do not reach sufficient values to overcome the resistance offered by the fibrillating myocardium. Interventions which increase IPP, intravascular pressures, and carotid flow do not improve CPP or, by inference, coronary flow.

Animals↗

PubMed2001

Analysis of the enzymatic domains in the modular portion of the coronafacic acid polyketide synthase.

Coronafacic acid (CFA) is the polyketide component of coronatine (COR), a phytotoxin produced by the plant pathogen Pseudomonas syringae. The CFA polyketide synthase (PKS) consists of two open reading frames (ORFs) that encode type I multifunctional proteins and several ORFs that encode monofunctional proteins. Sequence comparisons of the modular portions of the CFA PKS with other prokaryotic, modular PKSs elucidated the boundaries of the domains that are involved in the individual stages of polyketide assembly. The two beta-ketoacyl:acyl carrier protein synthase (KS) domains in the modular portion of the CFA PKS exhibit a high degree of similarity to each other (53%), but are even more similar to the KS domains of DEBS, RAPS, and RIF. Cfa6 possesses two acyltransferases- AT0, which is associated with a loading domain, and AT1, which uses ethylmalonyl-CoA (eMCoA) as a substrate for chain extension. Cfa7 contains an AT that uses malonyl-CoA as a substrate for chain extension. The Cfa6 AT0 shows 35 and 32% similarity to the DEBS1 and NidA1 AT0s, respectively, and 32 and 36% similarity to the Cfa6 and Cfa7 AT1s. Sequence motifs have previously been identified that correlate with AT substrates. The motifs in Cfa6 AT1 were found to correlate reasonably well with those predicted for methylmalonyl-CoA (mMCoA) ATs. The motifs in the AT of Cfa7 correlated more poorly with those predicted for MCoA ATs. Three ACP domains occur in the modular proteins of the COR PKS. The loading domain-associated ACP0 showed 38% similarity to the loading domain ACP0s of DEBS1 and NidA1 and 32-36% similarity to the two module-associated ACPs of the COR PKS. It exhibited a higher degree of similarity to the module-associated ACPs of RAPS. The two module-associated ACPs show 39% similarity to each other, but appear more closely related to module-associated ACP domains in RAPS and RIFS. Furthermore, the DH and KR domains of Cfa6 and Cfa7 show greater similarity to DH and KR domains in RAPS and RIFS than to each other. The CFA PKS includes a thioesterase domain (TE I) that resides at the C-terminus of Cfa7 and a second thioesterase, which exists as a separate ORF (Cfa9, a TE II). Analysis of a Cfa7 thioesterase mutant demonstrated that the TE domain is required for the production of CFA. The co-existence of TE domains within modular PKSs along with physically separated, monofunctional TEs (TE IIs) has been reported for a number of modular polyketide and non-ribosomal peptide synthases (NRPS). An analysis of the two types of thioesterases using Clustal X yielded a dendrogram showing that TE IIs from PKSs and NRPSs are more closely related to each other than to domain TEs from either PKSs or NRPSs. Furthermore, the dendrogram indicates that both types of TE IIs are more closely related to TE domains associated with PKSs than to TE domains in NRPSs. Finally, the overall % G+C content and the % G+C content at the third codon for all of the PKS genes in the COR cluster suggest that these genes may have been recruited from a gram-positive bacterium.

Acyl Carrier Protein↗

PubMed1998

Expression cloning in Fe2+ transport defective yeast of a novel maize MYC transcription factor.

A complementation approach of the yeast fet3fet4 mutant strain, defective in both low- and high-affinity iron transport, was initiated as an attempt to characterize the Fe(III)-mugineic acid (MA) transporter from grasses. A maize cDNA encoding a novel MYC transcription factor, named 7E, was cloned by screening an iron-deficient maize root cDNA expression library on a minimum media containing Fe(III)-deoxyMA as a unique iron source. 7E expression restored growth specifically to the fet3 fet4 mutant strain. It did not affect growth rate of a trk1trk2 potassium transport defective yeast strain or parental W303 strain growth rate. No 55Fe uptake increase was observed in 7E transformed fet3 fet4 yeast during short-term kinetics. However, the iron accumulation in these cells was 1.3-fold higher than in untransformed cells after a 24-h period. The 7E protein contained 694 amino acids and had a predicted molecular mass of 74.2kDa. It had 44% identity with the RAP-1 protein, a 67.9-kDa MYC-like protein from Arabidopsis thaliana which binds the G-box sequence via a basic region helix-loop-helix (bHLH), without requiring heterodimerization with MYB proteins. Phylogenic comparisons revealed that the maize 7E protein was related to the Arabidopsis thaliana RAP-1 protein and to the Phaseolus vulgaris PG1. This similarity was particularly evident for the bHLH domain, which was 95% identical between maize 7E and Arabidopsis thaliana RAP-1. 7E, RAP-1 and PG-1 proteins revealed a plant MYC-like sub-family that was more related to the maize repressor-like IN1 than to maize R proteins. 7E mRNA was detected in both roots and leaves by the Northern analysis. The amount of 7E mRNA increased, in response to iron starvation, by 20 and 40% in roots and leaves, respectively. The relationship between iron metabolism and myc expression in animal cells is discussed.

Amino Acid Sequence↗

PubMed1998

Identification and characterization of novel substrates of Trk receptors in developing neurons.

Neurotrophins influence growth and survival of specific populations of neurons through activation of Trks, members of the receptor tyrosine kinase (RTK) family. In this report, we describe the identification and characterization of two substrates of Trk kinases, rAPS and SH2-B, which are closely related Src homolog 2 (SH2) domain-containing signaling molecules. rAPS and SH2-B are substrates of TrkB and TrkC in cortical neurons and SH2-B is a substrate of TrkA in sympathetic neurons. Moreover, rAPS and SH2-B bind to Grb2, and both are sufficient to mediate NGF induction of Ras, MAP kinase (MAPK), and morphological differentiation of PC12 cells. Lastly, antibody perturbation and transient transfection experiments indicate that SH2-B, or a closely related molecule, is necessary for NGF-dependent signaling in neonatal sympathetic neurons. Together, these observations indicate that rAPS and SH2-B mediate Trk signaling in developing neurons.

Adaptor Proteins, Signal Transducing↗