Biomedical subjects

S Strack

Publications and source records attributed to S Strack.

At least 19 recordsLinked to original sources

PubMed2002

Tissue free water tritium and organically bound tritium in the rice plant acutely exposed to atmospheric HTO vapor under semi-outdoor conditions.

Potted rice plants were exposed to atmospheric HTO in a box outdoors for 1 h at 9 different times from booting to yellow-ripe stages. It is indicated that the leaf TFWT concentration may reach equilibrium within 1 h in clear weather. The plant TFWT concentration decreased at a rapid rate for the first several hours and at a much slower rate thereafter. The decrease till harvest was by factors of 600-95,000 depending on the plant parts and exposure times. The time course of the ear OBT concentration was characterized by the exposure time. After exposure at the booting to heading stages, the leaf OBT concentration decreased rapidly for the first several hours and then very slowly. The plant OBT concentration was initially about 2 orders of magnitude lower, but at harvest an order of magnitude higher, than the TFWT concentration. The OBT concentration in hulled seeds at harvest varied with exposure times by a factor of 70, being highest in the exposure performed at the earlier stage of rapid grain growth. Also in this exposure, the plant total OBT was greatest due to the seed OBT.

Environmental Exposure↗

PubMed2001

Is persistent activity of calcium/calmodulin-dependent kinase required for the maintenance of LTP?

Calcium/calmodulin-dependent protein kinase II (CaMKII) is concentrated in the postsynaptic density (PSD) and plays an important role in the induction of long-term potentiation (LTP). Because this kinase is persistently activated after the induction, its activity could also be important for LTP maintenance. Experimental tests of this hypothesis, however, have given conflicting results. In this paper we further explore the role of postsynaptic CaMKII in induction and maintenance of LTP. Postsynaptic application of a CaMKII inhibitor [autocamtide-3 derived peptide inhibitor (AC3-I), 2 mM] blocked LTP induction but had no detectable affect on N-methyl-D-aspartate (NMDA)-mediated synaptic transmission, indicating that the primary function of CaMKII in LTP is downstream from NMDA channel function. We next explored various methodological factors that could account for conflicting results on the effect of CaMKII inhibitors on LTP maintenance. In contrast to our previous work, we now carried out experiments at higher temperature (33 degrees C), used slices from adult animals, and induced LTP using a tetanic stimulation. However, we still found that LTP maintenance was not affected by postsynaptic application of AC3-I. Furthermore the inhibitor did not block LTP maintenance under conditions designed to enhance the Ca(2+)-dependent activity of protein phosphatases 1 and 2B (elevated Ca(2+), calmodulin, and an inhibitor of protein kinase A). We also tested the possibility that CaMKII inhibitor might not be able to affect CaMKII once it was inserted into the PSD. In whole-brain extracts, AC3-I blocked autophosphorylation of both soluble and particulate/PSD CaMKII with similar potencies although the potency of the inhibitor toward other CaMKII substrates varied. Thus we were unable to demonstrate a functional role of persistent Ca(2+)-independent CaMKII activity in LTP maintenance. Possible explanations of the data are discussed.

Animals↗

PubMed2001

Circular structure of the MCMI-III personality disorder scales.

Millon's (1987) circular model of personality disorders was examined in a large sample of psychiatric patients (N = 2,366) who completed the Millon Clinical Multiaxial Inventory-III (MCMI-III; Millon, 1997) as part of routine assessment after presentation for treatment. Principal components analyses were conducted to identify the first two dimensions in MCMI-III base rate scores, weighted and unweighted raw scores, and nonoverlapping scale scores. Similar analyses were made on these scores when acquiescence was partialled out. Circular plots of the scales were examined against Millon's hypothesized arrangement and the model was tested using confirmatory factor analysis. Results replicated those of Strack, Lorr, and Campbell (1990) with the MCMI-II. Millon's horizontal Impassive-Expressive dimension was recovered in both regular and residual scores but the vertical axis appeared to represent an Impulsivity-Compulsivity dimension rather than the Autonomous-Enmeshed continuum envisioned by Millon. Although scale order followed Millon's predictions for the most part, a number of departures from theoretical expectations were noted and none of the score sets yielded a good fit to the hypothetical structure. Millon's model appears to have promise as a circumplex that can encompass all of the personality disorders but changes are needed to rectify discrepancies between the theory and empirical findings.

Adolescent↗

PubMed2000

Association of calcium/calmodulin-dependent kinase II with developmentally regulated splice variants of the postsynaptic density protein densin-180.

In a continuing search for proteins that target calcium/calmodulin-dependent protein kinase II (CaMKII) to postsynaptic density (PSD) substrates important in synaptic plasticity, we showed that the PSD protein densin-180 binds CaMKII. Four putative splice variants (A-D) of the cytosolic tail of densin-180 are shown to be differentially expressed during brain development. Densin-180 splicing affects CaMKII phosphorylation of specific serine residues. Variants A, B, and D, but not C, bind CaMKII stoichiometrically and with high affinity, mediated by a differentially spliced domain. Densin-180 differs from the previously identified CaMKII-binding protein NR2B in that binding does not strictly require CaMKII autophosphorylation. Binding of densin-180 and NR2B to CaMKII is noncompetitive, indicating different interaction sites on CaMKII. Expression of the membrane-targeted CaMKII-binding domain of densin-180 confers membrane localization to coexpressed CaMKII without requiring calcium mobilization, suggesting that densin-180 plays a role in the constitutive association of CaMKII with PSDs.

Alternative Splicing↗

PubMed2000

Mechanism and regulation of calcium/calmodulin-dependent protein kinase II targeting to the NR2B subunit of the N-methyl-D-aspartate receptor.

Calcium influx through the N-methyl-d-aspartate (NMDA)-type glutamate receptor and activation of calcium/calmodulin-dependent kinase II (CaMKII) are critical events in certain forms of synaptic plasticity. We have previously shown that autophosphorylation of CaMKII induces high-affinity binding to the NR2B subunit of the NMDA receptor (Strack, S., and Colbran, R. J. (1998) J. Biol. Chem. 273, 20689-20692). Here, we show that residues 1290-1309 in the cytosolic tail of NR2B are critical for CaMKII binding and identify by site-directed mutagenesis several key residues (Lys(1292), Leu(1298), Arg(1299), Arg(1300), Gln(1301), and Ser(1303)). Phosphorylation of NR2B at Ser(1303) by CaMKII inhibits binding and promotes slow dissociation of preformed CaMKII.NR2B complexes. Peptide competition studies imply a role for the CaMKII catalytic domain, but not the substrate-binding pocket, in the association with NR2B. However, analysis of monomeric CaMKII mutants indicates that the holoenzyme structure may also be important for stable association with NR2B. Residues 1260-1316 of NR2B are sufficient to direct the subcellular localization of CaMKII in intact cells and to confer dynamic regulation by calcium influx. Furthermore, mutation of residues in the CaMKII-binding domain in full-length NR2B bidirectionally modulates colocalization with CaMKII after NMDA receptor activation, suggesting a dynamic model for the translocation of CaMKII to postsynaptic targets.

Amino Acid Sequence↗

PubMed2000

Transfection of nasal mucosa with a normal alpha1-antitrypsin gene in alpha1-antitrypsin-deficient subjects: comparison with protein therapy.

We sought to determine whether a normal alpha1-antitrypsin (AAT) gene could be expressed in respiratory epithelium and whether local expression would have antiinflammatory effects. In an unblinded study, we delivered a normal AAT gene in a plasmid-cationic liposome complex to one nostril of each of five subjects with AAT deficiency; the other, untreated nostril served as a control. AAT protein concentration in nasal lavage fluid (NALF) increased in the transfected nostril (TN), but not in the control nostril (CN), of every subject, peaking on day 5 at levels about one-third normal (baseline CN, 4.1 +/- 1.2 microg/mg of protein; baseline TN, 4.3 +/- 1.3; day 5 CN, 4.0 +/- 0.5 [p = NS versus baseline]; day 5 TN, 9.0 +/- 1.7 [p < 0.5 versus baseline]); isoelectric focusing identified the transgene-generated protein (M) in the only two patients in whom the measurement was possible. The reverse transcriptase-polymerase chain reaction (RT-PCR), performed on NALF from TN and CN of four of the five subjects, was positive for transgene message in TN in all cases and negative in NALF from CN except for one time point in one subject. Interleukin 8 (IL-8) concentrations in NALF were elevated at baseline (normal [N = 10] = 2.5 +/- 0.5 ng/mg of protein; baseline TN = 5.5 +/- 0.8, p < 0.05 versus normal) and decreased after AAT transfection (TN = 2.9 +/- 0.6, p < 0.05 versus baseline) but not in the control nostril (CN = 6.5 +/- 2.2, p = NS versus baseline). NALF samples taken from four of the patients while receiving intravenous AAT protein showed normal concentrations of AAT, but IL-8 concentrations (10.5 +/- 4.2 ng/mg of protein, p = NS versus baseline) were not decreased from baseline. We conclude that plasmid-cationic liposome delivery of a normal AAT gene to the respiratory epithelium of deficient patients produces potentially therapeutic local AAT concentrations and that AAT gene therapy, unlike AAT protein therapy, is antiinflammatory.

Administration, Intranasal↗

PubMed1999

Brain actin-associated protein phosphatase 1 holoenzymes containing spinophilin, neurabin, and selected catalytic subunit isoforms.

We previously characterized PP1bp134 and PP1bp175, two neuronal proteins that bind the protein phosphatase 1 catalytic subunit (PP1). Here we purify from rat brain actin-cytoskeletal extracts PP1(A) holoenzymes selectively enriched in PP1gamma(1) over PP1beta isoforms and also containing PP1bp134 and PP1bp175. PP1bp134 and PP1bp175 were identified as the synapse-localized F-actin-binding proteins spinophilin (Allen, P. B., Ouimet, C. C., and Greengard, P. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 9956-9561; Satoh, A., Nakanishi, H., Obaishi, H., Wada, M., Takahashi, K., Satoh, K., Hirao, K., Nishioka, H., Hata, Y., Mizoguchi, A., and Takai, Y. (1998) J. Biol. Chem. 273, 3470-3475) and neurabin (Nakanishi, H., Obaishi, H., Satoh, A., Wada, M., Mandai, K., Satoh, K., Nishioka, H. , Matsuura, Y., Mizoguchi, A., and Takai, Y. (1997) J. Cell Biol. 139, 951-961), respectively. Recombinant spinophilin and neurabin interacted with endogenous PP1 and also with each other when co-expressed in HEK293 cells. Spinophilin residues 427-470, or homologous neurabin residues 436-479, were sufficient to bind PP1 in gel overlay assays, and selectively bound PP1gamma(1) from a mixture of brain protein phosphatase catalytic subunits; additional N- and C-terminal sequences were required for potent inhibition of PP1. Immunoprecipitation of spinophilin or neurabin from crude brain extracts selectively coprecipitated PP1gamma(1) over PP1beta. Moreover, immunoprecipitation of PP1gamma(1) from brain extracts efficiently coprecipitated spinophilin and neurabin, whereas PP1beta immunoprecipitation did not. Thus, PP1(A) holoenzymes containing spinophilin and/or neurabin target specific neuronal PP1 isoforms, facilitating efficient regulation of synaptic phosphoproteins.

Amino Acid Sequence↗

PubMed1999

Cloning and characterization of B delta, a novel regulatory subunit of protein phosphatase 2A.

Variable regulatory subunits of protein phosphatase 2A (PP2A) modulate activity, substrate selectivity and subcellular targeting of the enzyme. We have cloned a novel member of the B type regulatory subunit family, B delta, which is most highly related to B alpha. B delta shares with B alpha epitopes previously used to generate subunit-specific antibodies. Like B alpha, but unlike B beta and B gamma which are highly brain-enriched, B delta mRNA and protein expression in tissues is widespread. B delta is a cytosolic subunit of PP2A with a subcellular localization different from B alpha and may therefore target a pool of PP2A holoenzymes to specific substrates.

Amino Acid Sequence↗

PubMed1999

Differential cellular and subcellular localization of protein phosphatase 1 isoforms in brain.

Protein phosphatase 1 (PP1) is a gene family with a number of important functions in brain. Association with a wide variety of regulatory/targeting subunits is thought to be instrumental in directing the phosphatase to specific subcellular locations and substrates. By using antibodies directed against specific PP1 isoforms, we asked whether PP1 isoforms are differentially distributed in brain. Immunoblotting detects in brain the PP1gamma2 isoform, which had previously been thought to be testis specific, in addition to alpha, beta, and gamma1 isoforms. PP1 isoform expression varies modestly in extracts from different subdissected brain regions and is relatively constant during postnatal development, except for an about twofold increase in PP1gamma2. By immunohistochemical analyses of rat brain, PP1beta and PP1gamma1 cellular expression is widespread but quite distinct from one another. Subcellular fractionation studies demonstrate that PP1beta and PP1gamma1 are selectively associated with different cytoskeletal elements: PP1beta with microtubules, PP1gamma1 with the actin cytoskeleton. Double-immunofluorescence labeling of cultured cortical neurons further reveals a strikingly different and nonoverlapping localization of PP1beta and PP1gamma1: whereas PP1beta localizes to a discrete area of the soma, PP1gamma1 is highly enriched in dendritic spines and presynaptic terminals of cultured neurons. These results show that PP1 isoforms are targeted to different neuronal cytoskeletal compartments with a high degree of specificity, presumably by isoform-specific association with regulatory/targeting proteins. Furthermore, the synaptic localization of PP1gamma1 indicates that it is this isoform that is involved in the regulation of synaptic phosphoproteins such as neurotransmitter receptors and ion channels implicated in synaptic plasticity.

Animals↗

PubMed1999

A study of Benjamin's eight-facet Structural Analysis of Social Behavior (SASB) model.

The study purpose was to evaluate the cluster, or facet, version of Benjamin's (1974, 1996b) Structural Analysis of Social Behavior (SASB) in independent samples of 133 normal participants and 182 psychiatric cases. We first tested for the presence of 3 circumplexes, Focus on the Other, Focus on the Self, and Introject in the 36 items that are hypothesized to define each of them. Next, intercorrelations of 8 item-based facet scales were assessed for internal consistency, factor structure, and circular order, with the expectation that the scales would be reliable, yield 2 higher-order factors, and demonstrate a circumplex structure. Principal components analysis was applied followed by varimax rotation. Data for both normal participants and patients uniformly confirmed the presence of 4 item-level factors and 2 cluster-based factors for each circle. Alpha coefficients for facet scales were typically high, but some were as low as .50. The principal difference between the normal participants and patients was that the circumplex was incomplete in the patient data with poor differentiation of the vertical and horizontal variables.

Adolescent↗

PubMed1999

Relating PACL measures of Millon's basic personality styles and MMPI-2 scales in patient and normal samples.

Millon's basic personality styles as measured by the Personality Adjective Check List (PACL; Strack, 1987, 1991b) were linked to Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) basic scales via bivariate correlation and factor analysis in independent samples of psychiatric patients (N = 196) and normal adults (N = 124). Consistent with previous research, Millon's neurotic, introverted styles were positively associated with MMPI-2 scales measuring introversion, affective states, and disturbed thinking, whereas extroverted, socially dominant Millon styles were negatively associated to the same scales. Millon personalities and MMPI-2 scales were reliably associated along two bipolar dimensions measuring Neuroticism/Introversion versus Extroversion and Emotional Distress versus Emotional Stability, which accounted for 45% of the variance. A third General Distress factor loaded only MMPI-2 scales. Congruency coefficients indicated that the factors for patients and normal participants were very similar. Results highlighted the consistency of the links between MMPI-2 basic scales, the PACL, and other Millon instruments, as well as the utility of the PACL as a measure of Millon's personality styles in a mental health population.

Adult↗

PubMed1999

Sadism and psychopathy in violent and sexually violent offenders.

A nonrandom sample (N = 41) of inmates from a maximum security prison were classified as either psychopathic or nonpsychopathic (using the Psychopathy Checklist-Revised (PCL-R)) and violent or sexually violent. Sadism was measured using the Millon Clinical Multiaxial Inventory-II (MCMI-II) Scale 6B, the Personality Disorder Examination (PDE) items for sadistic personality disorder, and the sexual sadism criteria of DSM-IV. Psychopaths were found to be significantly more sadistic than nonpsychopaths (MCMI-II and PDE). Overall power was relatively high. Sadism did not differentiate the violent and sexually violent groups. A diagnosis of sexual sadism was too infrequent (n = 3) for meaningful statistical analysis. The trait measures of sadism and psychopathy measures (PCL-R, Factor 1 and Factor 2) significantly and positively correlated. Results provide further empirical validity for the theoretically proposed and clinically observed relationship between sadistic traits and psychopathic personality.

Adult↗

PubMed1998

Autophosphorylation-dependent targeting of calcium/ calmodulin-dependent protein kinase II by the NR2B subunit of the N-methyl- D-aspartate receptor.

Activation and Thr286 autophosphorylation of calcium/calmodulindependent kinase II (CaMKII) following Ca2+ influx via N-methyl-D-aspartate (NMDA)-type glutamate receptors is essential for hippocampal long term potentiation (LTP), a widely investigated cellular model of learning and memory. Here, we show that NR2B, but not NR2A or NR1, subunits of NMDA receptors are responsible for autophosphorylation-dependent targeting of CaMKII. CaMKII and NMDA receptors colocalize in neuronal dendritic spines, and a CaMKII.NMDA receptor complex can be isolated from brain extracts. Autophosphorylation induces direct high-affinity binding of CaMKII to a 50 amino acid domain in the NR2B cytoplasmic tail; little or no binding is observed to NR2A and NR1 cytoplasmic tails. Specific colocalization of CaMKII with NR2B-containing NMDA receptors in transfected cells depends on receptor activation, Ca2+ influx, and Thr286 autophosphorylation. Translocation of CaMKII because of interaction with the NMDA receptor Ca2+ channel may potentiate kinase activity and provide exquisite spatial and temporal control of postsynaptic substrate phosphorylation.

Amino Acid Sequence↗

PubMed1998

Brain protein phosphatase 2A: developmental regulation and distinct cellular and subcellular localization by B subunits.

Protein phosphatase 2A (PP2A) is a heterotrimeric enzyme consisting of a catalytic subunit (C), a structural subunit (A), and a variable regulatory subunit (B). We have investigated the spatial and temporal expression patterns of three members of the B subunit family, Balpha, Bbeta, and Bgamma, both at the message level by using ribonuclease protection analysis and at the protein level by using specific antibodies. Although A, Balpha, and C protein are expressed in many tissues, Bbeta and Bgamma were detectable only in brain. Balpha, Bbeta, and Bgamma are components of the brain PP2A heterotrimer, because they copurified with A and C subunits on immobilized microcystin. Whereas Balpha and Bbeta are mainly cytosolic, Bgamma is enriched in the cytoskeletal fraction. In contrast to A, C, and Balpha, which are expressed at constant levels, Bbeta and Bgamma RNA and protein are developmentally regulated, with Bbeta levels decreasing and Bgamma levels increasing sharply after birth. RNA and immunoblot analyses of subdissected brain regions as well as immunohistochemistry demonstrated that B subunits are expressed in distinct but overlapping neuronal populations and cellular domains. These data indicate that B subunits confer tissue and cell specificity, subcellular localization, and developmental regulation to the PP2A holoenzyme. The Balpha-containing heterotrimer may be important in general neuronal functions that involve its partially nuclear localization. Holoenzymes containing B likely function in early brain development as well as in somata and processes of subsets of mature neurons. Bgamma may target PP2A to cytoskeletal substrates that are important in the establishment and maintenance of neuronal connections.

Amino Acid Sequence↗

PubMed1997

Carboxymethylation of nuclear protein serine/threonine phosphatase X.

Specific rabbit polyclonal antibodies against peptides corresponding to the highly homologous protein serine/threonine phosphatase 2A and X catalytic subunits (PP2A/C and PPX/C respectively) were used to investigate the cellular and subcellular distribution of PP2A/C and PPX/C, as well as their methylation state. Immunoblots of rat tissue extracts revealed a widespread distribution of these enzymes but particularly high levels of PP2A/C and PPX/C in brain and testes respectively. In addition, immunoblots of subcellular fractions and immunocytochemical analyses of rat brain sections demonstrated that PPX/C is predominantly localized to the nucleus, whereas PP2A/C is largely cytoplasmic. Treatment of nuclear extracts with alkali resulted in increased PPX/C immunoreactivity to a polyclonal antibody directed against the C-terminus; no change in PPX immunoreactivity was observed using an antibody against an internal peptide. Alkali treatment of brain and liver cytosolic and nuclear extracts did not change the molecular mass or the isoelectric point of PPX/C. Furthermore, tritiated PPX/C was immunoprecipitated from COS cell extracts incubated with the methyl donor S-adenosyl-l-[methyl-3H]methionine. Thus the increase in immunoreactivity probably results from removal of a carboxymethyl group from PPX/C, as has been shown previously for PP2A/C [Favre, Zolnierowicz, Turowski and Hemmings (1994) J. Biol. Chem. 269, 16311-16317]. Together, our results indicate that the PPX catalytic subunit is a predominantly nuclear phosphatase and is methylated at its C-terminus.

Amino Acid Sequence↗

PubMed1997

Protein serine/threonine phosphatase 1 and 2A associate with and dephosphorylate neurofilaments.

The phosphorylation state of neurofilaments plays an important role in the control of cytoskeletal integrity, axonal transport, and axon diameter. Immunocytochemical analyses of spinal cord revealed axonal localization of all protein phosphatase subunits. To determine whether protein phosphatases associate with axonal neurofilaments, neurofilament proteins were isolated from bovine spinal cord white matter by gel filtration. approximately 15% of the total phosphorylase a phosphatase activity was present in the neurofilament fraction. The catalytic subunits of PP1 and PP2A, as well as the A and B alpha regulatory subunits of PP2A, were detected in the neurofilament fraction by immunoblotting, whereas PP2B and PP2C were found exclusively in the low molecular weight soluble fractions. PP1 and PP2A subunits could be partially dissociated from neurofilaments by high salt but not by phosphatase inhibitors, indicating that the interaction does not involve the catalytic site. In both neurofilament and soluble fractions, 75% of the phosphatase activity towards exogenous phosphorylase a could be attributed to PP2A, and the remainder to PP1 as shown with specific inhibitors. Neurofilament proteins were phosphorylated in vitro by associated protein kinases which appeared to include protein kinase A, calcium/calmodulin-dependent protein kinase, and heparin-sensitive and -insensitive cofactor-independent kinases. Dephosphorylation of phosphorylated neurofilament subunits was mainly (60%) catalyzed by associated PP2A, with PP1 contributing minor activity (10-20%). These studies suggest that neurofilament-associated PP1 and PP2A play an important role in the regulation of neurofilament phosphorylation.

Amino Acid Sequence↗

PubMed1997

Translocation of autophosphorylated calcium/calmodulin-dependent protein kinase II to the postsynaptic density.

Calcium/calmodulin-dependent protein kinase II (CaMKII) undergoes calcium-dependent autophosphorylation, generating a calcium-independent form that may serve as a molecular substrate for memory. Here we show that calcium-independent CaMKII specifically binds to isolated postsynaptic densities (PSDs), leading to enhanced phosphorylation of many PSD proteins including the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-type glutamate receptor. Furthermore, binding to PSDs changes CaMKII from a substrate for protein phosphatase 2A to a protein phosphatase 1 substrate. Translocation of CaMKII to PSDs occurs in hippocampal slices following treatments that induce CaMKII autophosphorylation and a form of long term potentiation. Thus, synaptic activation leads to accumulation of autophosphorylated, activated CaMKII in the PSD. This increases substrate phosphorylation and affects regulation of the kinase by protein phosphatases, which may contribute to enhancement of synaptic strength.

Animals↗

PubMed1997

Differential inactivation of postsynaptic density-associated and soluble Ca2+/calmodulin-dependent protein kinase II by protein phosphatases 1 and 2A.

Autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) at Thr286 generates Ca2+-independent activity. As an initial step toward understanding CaMKII inactivation, protein phosphatase classes (PP1, PP2A, PP2B, or PP2C) responsible for dephosphorylation of Thr286 in rat forebrain subcellular fractions were identified using phosphatase inhibitors/activators, by fractionation using ion exchange chromatography and by immunoblotting. PP2A-like enzymes account for >70% of activity toward exogenous soluble Thr286-autophosphorylated CaMKII in crude cytosol, membrane, and cytoskeletal extracts; PP1 and PP2C account for the remaining activity. CaMKII is present in particulate fractions, specifically associated with postsynaptic densities (PSDs); each protein phosphatase is also present in isolated PSDs, but only PP1 is enriched during PSD isolation. When isolated PSDs dephosphorylated exogenous soluble Thr286-autophosphorylated CaMKII, PP2A again made the major contribution. However, CaMKII endogenous to PSDs (32P autophosphorylated in the presence of Ca2+/calmodulin) was predominantly dephosphorylated by PP1. In addition, dephosphorylation of soluble and PSD-associated CaMKII in whole forebrain extracts was catalyzed predominantly by PP2A and PP1, respectively. Thus, soluble and PSD-associated forms of CaMKII appear to be dephosphorylated by distinct enzymes, suggesting that Ca2+-independent activity of CaMKII is differentially regulated by protein phosphatases in distinct subcellular compartments.

Animals↗