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PubMed2004

Somatoform dissociation, reported abuse and animal defence-like reactions.

OBJECTIVE: To test the hypotheses that among general psychiatric outpatients, somatoform dissociation is associated with posttraumatic stress symptoms and with reported potentially traumatizing events, especially with events that involve bodily threat from a person, also when reported age at onset, duration and subjectively rated impact of potentially traumatizing events are considered. METHOD: Administration of self-report questionnaires evaluating the severity of somatoform and psychoform dissociation, posttraumatic stress-symptoms, and reported traumatizing events, using samples of consecutive and unselected psychiatric outpatients (n = 153). RESULTS: Somatoform dissociation was strongly correlated with posttraumatic stress symptoms and with reported cumulative traumatization as assessed with two different self-report trauma questionnaires. Among a wide range of trauma types, bodily threat from a person best predicted somatoform dissociation. Emotional neglect and age further improved the prediction, but emotional neglect and abuse did not predict somatoform dissociation when interpersonal threat to the body was not reported. Somatoform dissociation was also best predicted by bodily threat when reported age at onset, duration and subjective impact of reported traumatization were included in the analyses. CONCLUSION: This retrospective study suggests that recurrent interpersonal bodily threat may evoke animal defence-like psychobiological systems manifesting as somatoform dissociation and that this type of threat is often accompanied by emotional neglect. These hypotheses should now be tested in prospective studies.

Adolescent↗
PubMed1978

Protein dissociation from DNA in model systems and chromatin.

Salt induced dissociation of protamine, poly(L-lysine) and poly(L-arginine) from DNA was measured by relative light scattering at theta = 90 degrees and/or centrifugation. Dissociation of histones from DNA was studied using relative light scattering and intrinsic tyrosine fluorescence. Protamine was dissociated from DNA at 0.15 M MgCl2 (ionic strength mu = 0.45) or 0.53 M NaCl (mu = 0.53) based on light scattering data and at approximately 0.2 M MgCl2 (mu = 0.6) or 0.6 M NaCl based on centrifugation data. NaCl induced dissociation of poly(Lys) or poly(Arg) from natural DNAs measured by light scattering did not depend on the guanine plus cytosine content. To dissociate poly(Arg) from DNA higher ionic strength using NaCl, MgCl2, or CaCl2, similar ionic strength using NaClo4, and lower ionic strength using Na2SO4 was needed then to dissociated poly(Lys). Both the decrease in light scattering and the enhancement of tyrosine fluorescence of chromatin occurred between 0.5 and 1.5 M NaCl when histones were dissociated.

Anions↗
PubMed2001

Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation.

Calpain is a heterodimeric, intracellular Ca(2+)-dependent, "bio-modulator" that alters the properties of substrates through site-specific proteolysis. It has been proposed that calpains are activated by autolysis of the N-terminus of the large subunit and/or its dissociation into the subunits. It is, however, unclear whether the dissociation into subunits is required for the expression of protease activity and/or for in vivo function. Recently, the crystal structure of m-calpain in the absence of Ca(2+) has been resolved. The 3D structure clearly shows that the N-terminus of the m-calpain large subunit (mCL) makes contact with the 30K subunit, suggesting that autolysis of the N-terminus of mCL changes the interaction of both subunits. To examine the relationship between autolysis, dissociation, and activation, we made and analysed a series of N-terminal mutants of mCL that mimic the autolysed forms or have substituted amino acid residue(s) interacting with 30K. As a result, the mutant m-calpains, which are incapable of autolysis, did not dissociate into subunits, whereas those lacking the N-terminal 19 residues (Delta 19), but not those lacking only nine residues (Delta 9), dissociated into subunits even in the absence of Ca(2+). Moreover, both Delta 9 and Delta 19 mutants showed an equivalent reduced Ca(2+) requirement for protease activity. These results indicate that autolysis is necessary for the dissociation of the m-calpain subunits, and that the dissociation occurs after, but is not necessary for, activation.

Amino Acid Motifs↗
PubMed1983

Studies on the high molecular weight form of polypeptide chain elongation factor-1 from pig liver. III. Temperature-dependent dissociation into subunits in the presence of GTP.

Dissociation of highly purified EF-1 alpha beta gamma (a high molecular weight form of polypeptide chain elongation factor-1) from pig liver into EF-1 alpha and EF-1 beta gamma at various temperatures was examined and the following results were obtained. (i) When dissociation of EF-1 alpha beta gamma was analyzed by gel filtration with Sephacryl S-200, it was found that in the absence of GTP, it did not dissociate at any temperature between 4 and 37 degrees C, whereas in the presence of GTP, it tended to dissociate with elevation of the temperature, and almost complete dissociation was observed at 32 degrees C. This indicated that the dissociation constant of EF-1 alpha beta gamma into EF-1 alpha and EF-1 beta gamma in the presence of GTP increased with increase in the temperature. (ii) When gel filtration was performed in the presence of both GTP and [14C]Phe-tRNA, the formation of a ternary complex of EF-1 alpha . GTP . [14C]Phe-tRNA from EF-1 alpha beta gamma was noted, and its amount was found to increase with elevation of the temperature. (iii) The amount of [14C]Phe-tRNA bound to ribosomes dependent on added EF-1 alpha beta gamma similarly increased with increase in the temperature, as in the case of ternary complex formation, whereas the binding of [14C]Phe-tRNA to ribosomes dependent on free EF-1 alpha proceeded fairly well even at 0 degrees C. From these results we concluded that among the reaction steps in the binding of [14C]Phe-tRNA to ribosomes dependent on EF-1 alpha beta gamma, dissociation of EF-1 alpha beta gamma to form EF-1 alpha . GTP and EF-1 beta gamma in the presence of GTP is the step which is strongly influenced by temperature.

Animals↗
PubMed1977

Association-dissociation and denaturation behaviour of an oligomeric seed protein alpha-globulin of Sesamum indicum L. in acid and alkaline solutions.

The association-dissociation and denaturation behaviour of the major protein fraction, alpha-globulin of sesame seed (Sesamum indicum L.), in acid and alkaline solutions in the ranges of pH 4.2-1.5 and pH 7-12 have been studied. The results of gel filtration, fluorescence and viscosity measurements indicate dissociation and denaturation of the protein up to pH approximately 3. The difference spectrum in this region arises from a combination of dissociation, denaturation and charge effect on the chromophore. In still stronger acid solution, reassociation of the dissociated fraction takes place by hydrophobic interaction. In alkaline solution dissociation takes place around pH 8, and above pH 10 dissociation and denaturation proceed simultaneously as has been evidenced by sedimentation, fluorescence, spectral change, optical rotation and viscosity measurements. The phenolic group (pKInt=10.6) in the protein is abnormal and denaturation in alkaline solution is irreversible. Above pH 11.5 further dissociation of the protein takes place. Characteristic pH values of transition from 10.6-10.8 indicate that the transition of the protein involves a single step in alkaline solution.

Acids↗
PubMed1988

Carbamoyl-phosphate synthetase I. Kinetics of binding and dissociation of acetylglutamate and of activation and deactivation.

The dissociation of the cofactor, acetylglutamate, from the enzyme-cofactor complex formed by carbamoyl-phosphate synthetase I of rat liver in the presence of ATP, Mg2+, K+ and HCO-3 has been studied by centrifugal gel filtration. The rate of its dissociation (k, 0.13 s-1) is considerably slower than the rate of enzyme turnover (approximately equal to 6 s-1) and it is not increased by ammonia, although ammonia reduces the rate of reassociation of the cofactor. Omission of ATP, Mg2+ or K+ from the column buffer leads to virtually complete dissociation of bound acetylglutamate during passage through the column (0.5-2 min), owing to an increase in dissociation and a decrease in reassociation, but reduction of free Mg2+ alone has the opposite action. Dilution of the enzyme-cofactor complex into a large volume of buffer causes a biphasic loss of enzyme activity with a t1/2 of the first phase comparable with that of the dissociation of acetylglutamate. These findings show (a) that acetylglutamate does not dissociate with each turnover of the enzyme; (b) that there are rapid interactions between binding of acetylglutamate and ATPA (ATPA yields Pi in the overall reaction), Mg2+ and K+, suggesting that these ligands bind in close proximity; and (c) that the enzyme transiently retains considerable activity after dissociation of the cofactor.

Adenosine Triphosphate↗
PubMed1988

DNA-binding properties of gene-5 protein encoded by bacteriophage M 13. 1. The kinetics of the dissociation of gene-5-protein.polynucleotide complexes upon addition of salt.

The irreversible dissociation kinetics of complexes of M13-encoded gene-5 protein with the polynucleotides poly(dA) and M13 DNA was studied by means of stopped-flow experiments. A linear decay was found for all gene-5-protein.poly(dA) complexes and for the gene-5-protein.M13 DNA complexes for which the DNA lattice was completely saturated at the beginning of the dissociation experiments. Only at the end of the dissociation curve was a deviation from linearity observed. A single-exponential decay was found for the dissociation of gene-5-protein.M13 DNA complexes when the DNA was not completely saturated initially. These results could be interpreted by assuming that dissociation of bound protein is only possible from isolated binding sites, while during the dissociation, rearrangement of bound protein clusters takes place continuously, including the formation of newly isolated bound protein. This redistribution results from a translocation of the protein along the lattice, which, for the poly(dA) complex, is fast with respect to the dissociation step, but which is slow for the M13 DNA complex. During this process the equilibrium cluster distribution predicted by the theory of McGhee and Von Hippel is not maintained. The binding of gene-5 protein to poly(dA) or poly(dT) does not result in a broadening of the nucleotide resonances in the NMR spectra of these polynucleotides, as had been observed for E. coli DNA-binding protein and interpreted as an indication for a high rate of translocation of the protein on the polynucleotide. The absence of line broadening for gene-5-protein.polynucleotide complexes is caused by the high binding cooperativity. As a consequence the majority of the protein molecules are bound in a cluster which makes the concentration of isolated bound protein very low. This results in a decrease of the signal/noise ratio at higher degrees of binding, but does not lead to line broadening while fast translocation still occurs.

Binding, Competitive↗
PubMed1990

The H(+)-induced dissociation of human plasma alpha 2-macroglobulin. An investigation using small-angle neutron scattering and test of trypsin binding activity.

The dissociation of the tetrameric alpha 2-macroglobulin molecule into two half-molecular fragments, which occurs at pH less than 4.5, has been investigated using the small-angle neutron scattering method, and test of trypsin binding activity. Best fit with the relative forward scattering of neutrons is obtained for a model where the dissociation of the protein is driven by the uptake of H+ on altogether four acid-base groups, one per monomeric subunit of alpha 2-macroglobulin. These groups are not (or only slightly) accessible in the native tetramer, but become exposed to the solvent after dissociation of the protein. The H(+)-binding constant obtained for these groups, after dissociation of the protein, log K1 in the range 4.2-4.5, suggests that they are most probably carboxylate groups. From the about 10% increase in the radius of gyration, which occurs when lowering the pH from 4.5 to 2.0, we can conclude that the dissociation is associated with a change in structure of the protein. Tests of trypsin binding show that there is also an irreversible loss in trypsin binding activity, which is directly related to the fraction of dissociated protein. Thus, at pH less than 4.5, there is a transition of alpha 2-macroglobulin which results simultaneously in dissociation, disorganisation of the conformation of the subunits and loss in activity.

Binding Sites↗
PubMed1994

Dissociation of pigeon-liver malic enzyme in reverse micelles.

Pigeon-liver malic enzyme has a tendency to aggregate at a large concentration of protein. The larger aggregates (hexamer and octamer) were demonstrated to be enzymically active with specific activity similar to that of the tetramer. When the enzyme was embedded in a reverse micellar system prepared by dissolving the surfactant sodium bis(2-ethylhexyl)-sulfosuccinate (AOT) in isooctane, the tetrameric enzyme dissociated into monomers. The dissociated monomers were also enzymically active but with diminished specific activity relative to the activity in aqueous media. The decreased enzyme activity in reverse micelles was due to interactions of surfactant with the enzyme molecules, suggesting that the cytosolic malic enzyme is located near the plasma membrane. When the dissociation was monitored by altering the degree of hydration of the system (represented by the ratio [H2O]/[AOT]), the detergent and organic solvent slightly affected KTD, the dissociation constant of tetramer to dimers (T <--> 2 D), but increased KDM, the dissociation constant of dimer to monomers (D <--> 2 M), by 1-2 orders of magnitude; this change caused a 2-3 orders of magnitude increase in the overall dissociation constant KTM (T <--> 4 M). The dissociation of the tetrameric malic enzyme to monomers was favored by approximately 16 kJ/mol in AOT/isooctane reverse micelles versus aqueous media. We propose water-shell and induced-fit models for the enzyme in AOT/isooctane reverse micelles at large and small [H2O]/[AOT] ratios to explain this data, respectively. The asymmetric quaternary structure of the enzyme [Lee, H. J. & Chang, G. G. (1990) FEBS Lett. 277, 175-179] was re-evaluated in terms of the subunit interactions and various interconvertible enzyme forms.

Animals↗
PubMed1986

Binding sites for [3H]cocaine in mouse striatum and cerebral cortex have different dissociation kinetics.

[3H]Cocaine dissociates from its binding sites in the mouse cerebral cortex with a half-time of 25 s. The dissociation kinetics in the striatum is consonant with the presence of two populations of sites with dissociation half times of 2 s and 27 s, comprising 88% and 12%, respectively, of the total binding sites. On the basis of previous pharmacological characterization of [3H]cocaine binding, we propose that the slowly dissociating component represents the sites associated with 5-hydroxytryptamine (serotonin) uptake, and the rapidly dissociating component the 3,4-dihydroxyphenylethylamine (dopamine)-related sites. Evidence is presented that the extremely high dissociation rates do not preclude the measurement of [3H]cocaine binding by rapid filtration. The dissociation of [3H]cocaine from cerebrocortical membranes is slowed to a small but statistically significant extent by serotonin.

Animals↗
PubMed1981

High frequency fo X-Y chromosome dissociation in primary spermatocytes of F1 hybrids between Japanese wild mice (Mus musculus molossinus) and inbred laboratory mice.

In the hybrids between Japanese wild mice (Mus musculus molossinus) and inbred laboratory mice (BALB/c and B10.BR, which were probably derived from M. m. domesticus), the X and Y chromosomes dissociated precociously at the first meiotic metaphase in some 70% of spermatocytes; that percentage was only 8.9% in inbred laboratory mice and 21.1% in wild mice. X-Y dissociation began at least at early diakinesis and continued during metaphase I (MI). Some autosomes of the hybrid (10.1%) and BALB/c (10.6%) mice also dissociated precociously, but there was no distinctive correlation between X-Y and autosomal dissociation. In B10 or B6 congenic lines with a Y chromosome from wild M. m. molossinus, there was an apparent tendency for the percentage of precocious X-Y dissociation to decrease with an increasing number of back cross generations. Based on these observations we concluded that: 1. the X-Y dissociation found is genetically controlled, perhaps by multiple genes; 2. these genes are located on autosomes and are active only when they are heterozygous; 3. the frequent dissociation of the sex chromosomes neither affects male fertility nor induces non-disjunction of the X and Y chromosomes, though it significantly reduces testes weight.

Animals↗
PubMed1983

Intracellular pharmacokinetics of methotrexate polyglutamates in human breast cancer cells. Selective retention and less dissociable binding of 4-NH2-10-CH3-pteroylglutamate4 and 4-NH2-10-CH3-pteroylglutamate5 to dihydrofolate reductase.

Methotrexate (MTX-Glu1) exerts its antitumor effects through its potent inhibition of dihydrofolate reductase (DHFR), the enzyme responsible for maintaining the cellular pool of reduced folates. Since the drug-enzyme complex (bound drug) is slowly dissociable, an excess of drug (unbound or free drug) above that required to bind all enzyme sites is required in order to compete with substrate for sites made available by enzyme-drug dissociation. We have examined the role of the polyglutamyl metabolites of MTX-Glu1 containing two to five glutamyl (MTX-Glu2-5) groups in gamma peptide linkage in maintaining an intracellular pool of free drug and in forming slowly dissociable complexes with DHFR. During 24-h incubations of ZR-75-B human breast cancer cells with 2 microM MTX-Glu1, we observed the progressive formation of derivatives with two to five glutamyl groups, which rapidly replaced the parent compound on enzyme binding sites and represented 85% of both unbound and bound intracellular drug at the end of incubation. When cells were then placed in drug-free medium, the rates of disappearance of drug and metabolites from the intracellular bound and free fractions decreased with increasing glutamyl chain length. Over 90% of both bound and free MTX-Glu1 left the cells within 1 h, greater than 90% of MTX-glu2 left within 6 h, and greater than 90% of MTX-Glu3 left the bound and free fractions within 24 h. In contrast, free MTX-Glu4 fell by only 63% and bound by only 23% after 24 h, while free MTX-Glu5 increased by 52% after 6 h in drug-free medium and bound MTX-Glu5 increased threefold after 24 h, as it replaced the other forms of drug bound to DHFR. These results suggested a rapid dissociation of MTX-GLu1 and -Glu2 from the enzyme, and a slower dissociation of the longer chain length derivatives. This conclusion was confirmed by examining the rates at which [3H]MTX-Glu1 through -Glu5 could be replaced on enzyme binding sites by a fivefold or greater excess of unlabeled MTX-Glu1. Bound [3H]MTX-Glu1 and -Glu2 had dissociation t 1/2 of 12 and 30 min, respectively, while -Glu3, -Glu4, and -Glu5 had t 1/2 of 102, 108, and 120 min. These experiments demonstrated that the longer chain polyglutamates have prolonged intracellular retention and can be dissociated less readily than MTX-Glu2 from DHFR, properties likely to make them more efficient DHFR inhibitors than the parent drug and of potential importance in extending the duration of drug action in tumor cells.

Binding Sites↗
PubMed1987

Uptake of oleate from albumin solutions by rat liver. Failure to detect catalysis of the dissociation of oleate from albumin by an albumin receptor.

The hepatic removal of albumin-bound substances from plasma requires that they dissociate from albumin. Using indirect methods, we and others have proposed that dissociation may be catalyzed by interaction of albumin with the liver cell surface. This study looked for direct evidence of catalysis by comparing the rate of dissociation of oleate from albumin in vitro with the rate observed within the sinusoids of perfused rat liver. No evidence for catalysis was found. The rate of hepatic oleate removal from dilute albumin solutions did not exceed but instead closely paralleled the rate predicted from the in vitro dissociation rate constant (0.14s-1). These results suggest that under some conditions the liver can remove unbound material from the sinusoids faster than it can be replenished by dissociation from albumin, resulting in dissociation-limited removal. However, dissociation of oleate does not appear to be catalyzed by the liver.

Albumins↗
PubMed1995

Specificity of ligand-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability.

The molecular basis for the different physiological effects of testosterone (T) and dihydrotestosterone (DHT) was investigated using recombinantly expressed wild-type and mutant androgen receptor (AR). Rates of androgen dissociation from nuclear and cytoplasmic AR were compared with hormone- and concentration-dependent receptor degradation rates. T dissociates from AR 3 times faster than DHT or methyltrienolone (R1881) and is less effective in stabilizing the receptor. Analysis of AR deletion mutants and AR/glucocorticoid receptor chimeras indicates that the AR NH2-terminal domain has a specific role in stabilizing the receptor by slowing the rate of ligand dissociation and AR degradation. Amino acid mutations that abolish receptor dimerization, nuclear localization, or DNA-binding activity have no significant effect on androgen dissociation or AR degradation. A naturally occurring steroid-binding domain mutation (Val889 to Met) that causes androgen insensitivity, but does not alter equilibrium androgen binding affinity, lowered the androgen-binding capacity as a result of increased rates of androgen dissociation and AR degradation. Thus, AR stabilization and function require prolonged receptor occupancy with androgen, with a similar extent of stabilization observed at higher concentrations of faster dissociating androgens and lower concentrations of slower dissociating androgens. Retention of receptor-bound androgen is enhanced by an interaction between the AR NH2-terminal and steroid-binding domains. The ligand specificity and concentration dependence of receptor stabilization provide an explanation for physiological differences in the actions of T and DHT.

Animals↗
PubMed1987

Dissociation and reassociation of trichocyst proteins: biochemical and ultrastructural studies.

Trichocysts, the crystalline exocytotic organelles in Paramecium tetraurelia, are composed of small, acidic proteins existing primarily as disulphide-linked dimers. We have disaggregated trichocyst proteins with heat, simultaneously observing the changes in morphology and protein composition. The tip matrix was most heat-labile; its subunits progressively broke away from the distal end. During this process, breakdown of the cylindrical shaft began. Shafts first became flattened and torn lengthwise, yielding smaller, interconnected pieces still having the crystalline arrangement of their 5 nm thick fibres. Ultimately this pattern became disordered, and discrete fibrils of the same thickness disengaged from the meshwork. In freeze-etched preparations these fibrils were composed of thinner filaments in side-by-side association. Disaggregation of the tip sheath began from the distal end before shaft dissociation was complete. Trichocysts broke down to thin fibrils, but probably not to monomeric subunits. At least three proteins were preferentially released in the initial phase of dissociation. Disulphide-reducing agent present during heating increased the rate of dissociation without altering the sequence of morphological changes or the order of release of individual proteins. The rate and extent of heat-induced dissociation were strongly dependent on pH and cation concentration. The stabilizing effects of low pH and of cations were additive. A cooled suspension of fully dissociated trichocysts reassociated into sedimentable aggregates with discernible filamentous order, but without the crystalline structure of intact trichocysts. Reassociation was dependent upon time, temperature and protein concentration. All but one of the trichocyst proteins re-entered the sedimentable aggregate during reassociation. Reassociation was faster and more complete at pH 6 than at pH 8 and was stimulated by Ca2+, Mg2+ and La3+. Trichocyst proteins dissociated in the presence of dithiothreitol did not reassociate, even after removal of the reducing agent. Trichocysts from mutants defective to varying degrees in trichocyst formation were subjected to similar experimental protocols. Heat-dissociated trichocysts of the mutants scc6 and ptA1 reassociated at rates similar to those of wild-type; ftA3 showed slower reassociation, and tam38 showed little or no reassociation. Reassociation of wild-type trichocyst proteins was blocked by the addition of an equal amount of tam38 trichocyst proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

The role of ribosome recycling factor in dissociation of 70S ribosomes into subunits.

Protein synthesis is initiated on ribosomal subunits. However, it is not known how 70S ribosomes are dissociated into small and large subunits. Here we show that 70S ribosomes, as well as the model post-termination complexes, are dissociated into stable subunits by cooperative action of three translation factors: ribosome recycling factor (RRF), elongation factor G (EF-G), and initiation factor 3 (IF3). The subunit dissociation is stable enough to be detected by conventional sucrose density gradient centrifugation (SDGC). GTP, but not nonhydrolyzable GTP analog, is essential in this process. We found that RRF and EF-G alone transiently dissociate 70S ribosomes. However, the transient dissociation cannot be detected by SDGC. IF3 stabilizes the dissociation by binding to the transiently formed 30S subunits, preventing re-association back to 70S ribosomes. The three-factor-dependent stable dissociation of ribosomes into subunits completes the ribosome cycle and the resulting subunits are ready for the next round of translation.

Escherichia coli↗
PubMed2005

Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2.

Cohesin is a protein complex that is required to hold sister chromatids together. Cleavage of the Scc1 subunit of cohesin by the protease separase releases the complex from chromosomes and thereby enables the separation of sister chromatids in anaphase. In vertebrate cells, the bulk of cohesin dissociates from chromosome arms already during prophase and prometaphase without cleavage of Scc1. Polo-like kinase 1 (Plk1) and Aurora-B are required for this dissociation process, and Plk1 can phosphorylate the cohesin subunits Scc1 and SA2 in vitro, consistent with the possibility that cohesin phosphorylation by Plk1 triggers the dissociation of cohesin from chromosome arms. However, this hypothesis has not been tested yet, and in budding yeast it has been found that phosphorylation of Scc1 by the Polo-like kinase Cdc5 enhances the cleavability of cohesin, but does not lead to separase-independent dissociation of cohesin from chromosomes. To address the functional significance of cohesin phosphorylation in human cells, we have searched for phosphorylation sites on all four subunits of cohesin by mass spectrometry. We have identified numerous mitosis-specific sites on Scc1 and SA2, mutated them, and expressed nonphosphorylatable forms of both proteins stably at physiological levels in human cells. The analysis of these cells lines, in conjunction with biochemical experiments in vitro, indicate that Scc1 phosphorylation is dispensable for cohesin dissociation from chromosomes in early mitosis but enhances the cleavability of Scc1 by separase. In contrast, our data reveal that phosphorylation of SA2 is essential for cohesin dissociation during prophase and prometaphase, but is not required for cohesin cleavage by separase. The similarity of the phenotype obtained after expression of nonphosphorylatable SA2 in human cells to that seen after the depletion of Plk1 suggests that SA2 is the critical target of Plk1 in the cohesin dissociation pathway.

Amino Acid Substitution↗
PubMed1996

Prolactin causes the dissociation of prolactin from plasma membrane receptor in lactating mouse mammary cell: action of high prolactin concentration.

In order to characterize the dissociation of receptor-bound prolactin (PRL) by mammary cells, cells were prepared from lactating mice by collagenase digestion and loaded with PRL. The dissociation reaction was performed in the presence of PRL. In the concentration range 1 ng/ml-1 micrograms/ml examined, PRL at higher than 10 ng/ml accelerated the dissociation of PRL in an concentration-dependent manner. The action of PRL on dissociation was completed within a short period. At the end of the 1 h-incubation period, the dissociation rate constant (k-1) was about 2 times larger in the presence of 1 microgram/ml of PRL than in its absence. The action of PRL occurred predominantly at the level of the plasma membrane receptor. Mammary cells with greater PRL-binding capacities had larger k-1 in response to PRL. The present data showed that the dissociation of PRL from the receptor was influenced by the concentration or PRL and by the PRL-binding capacity of the cell. The rate of PRL-receptor interaction is expressed by the equation of k-1 (PRL-bound receptors). It is probable that the exceedingly high levels of PRL, the PRL-receptor interaction occurs more frequently in the presence of PRL-dependent dissociation than in its absence.

Acetic Acid↗