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S D Yang

Publications and source records attributed to S D Yang.

At least 73 records · Page 4Linked to original sources
PubMed1992

Identification of the ATP.Mg-dependent protein phosphatase activator (FA) as a synapsin I kinase that inhibits cross-linking of synapsin I with brain microtubules.

The ATP.Mg-dependent protein phosphatase activating factor (FA) has been identified and purified to near homogeneity from brain. In this report, as evidenced on SDS-polyacrylamide gel electrophoresis followed by autoradiography, factor FA has further been identified as a cAMP and Ca(2+)-independent brain kinase that could phosphorylate synapsin I, a neuronal protein that coats synaptic vesicles, binds to cytoskeleton, and is believed to be involved in the modulation of neurotransmission. Kinetic study further indicated that factor FA could phosphorylate synapsin I with a low Km value of about 2 microM and with a molar ratio of 1 mol of phosphate per mole of protein. Peptide mapping analysis revealed that factor FA specifically phosphorylated the tail region of synapsin I but on a unique site distinct from those phosphorylated by Ca2+/calmodulin-dependent protein kinase II and cAMP-dependent protein kinase, the two well-established synapsin I kinases. Functional study further revealed that factor FA could phosphorylate this unique specific site on the tail region of synapsin I and thereby inhibit cross-linking of synapsin I with microtubules. The results further suggest the possible involvement of factor FA as a synapsin I kinase in the regulation of axonal transport process of synaptic vesicles via the promotion of vesicles motility during neurotransmission.

Adenosine Triphosphate↗
PubMed1992

Dimethylnitrosamine (DMN)-induced IL-1 beta, TNF-alpha, and IL-6 inflammatory cytokine expression.

Altered immune functions have been demonstrated in mice following exposure to dimethylnitrosamine (DMN). In particular, changes in cell-mediated immune responses resulted from chronic DMN exposure in vivo. Since cytokines are potent immunoregulatory peptides, experiments were performed to determine whether DMN exposure results in the induction of serum-borne inflammatory cytokines. Animals were exposed to either vehicle (PBS) or DMN (5.0 mg/kg) every 24 hr for 14 days. Serum and liver samples were obtained from individual mice at 0, 1, 2, 3, 6, 12, and 24 hr following the first exposure, with additional samples collected every 24 hr preceding the daily DMN exposure. Sera were then analyzed for IL-1 beta, IL-3, IL-6, CSF-1, GM-CSF, and TNF-alpha activities using either biological or immunological assays. In addition, liver total cellular RNA was probed for the induction of IL-1 beta transcripts using the solution hybridization/RNase protection assay. IL-1 beta, IL-6, and TNF-alpha serum activities were observed within 2 hr of DMN exposure and returned to vehicle control levels by 3 days even though DMN exposure was maintained. Chronic expression of cytokine activity (after 72 hr) was only observed for GM-CSF. A rapid induction of IL-1 beta transcripts (within 1 hr) in both vehicle and DMN-treated animals was observed by solution hybridization. However, by 3 hr postexposure, transcript levels decreased in the vehicle-treated animals while remaining elevated in the DMN-treated animals for 6 hr. These results demonstrated that DMN exposure in vivo induced: (1) the expression of serum-borne cytokine activities, and (2) IL-1 beta transcription in liver tissue.

Animals↗
PubMed1992

Dysfunction of insulin mediator protein kinase FA in lymphocytes of patients with NIDDM.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) had an impaired capability to activate exogenous ATP.Mg-dependent protein phosphatase in lymphocytes compared with nondiabetic subjects. More importantly, the impaired protein phosphatase activation in the lymphocytes of patients with NIDDM could be consistently and completely restored to normal by exogenous pure protein kinase FA (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in patients with NIDDM is due to a functional loss of kinase FA. By contrast, both NIDDM patients and nondiabetic subjects had similar levels of total cell proteins and spontaneously active protein phosphatase activity in their lymphocytes, indicating that the dysfunction of kinase FA in patients with NIDDM is very specific. Statistical analysis further revealed that the lymphocytes isolated from 21 nondiabetic subjects contained high levels of FA activity (148 +/- 22 mU/mg cell protein), whereas, the lymphocytes of 21 patients with NIDDM contained low levels of FA activity (50 +/- 22 mU/mg), indicating statistically significant differences in FA activity between diabetic patients and nondiabetic subjects. This is the first report providing initial evidence that patients with NIDDM may statistically have a common impairment in the protein phosphatase activation in their lymphocytes and that the molecular mechanism for this defect is due to a biochemical dysfunction of protein kinase FA, a biological mediator for both insulin and epidermal growth factor.

Adult↗
PubMed1991

Cyclic phosphorylation-dephosphorylation of rhodopsin in retina by protein kinase FA (the activator of ATP.Mg-dependent protein phosphatase).

The ATP.Mg-dependent protein phosphatase activating factor (protein kinase FA) was identified to exist in bovine retina. Furthermore, rhodopsin, the visual light pigment associated with rod outer segments in retina, could be well phosphorylated by kinase FA to about 0.9 mol of phosphates per mol of protein. Moreover, more than 90% of the phosphates in [32P]-rhodopsin could be completely removed by ATP.Mg-dependent protein phosphatase and the rhodopsin phosphatase activity was strictly kinase FA-dependent. Taken together, the results provide initial evidence that a cyclic phosphorylation-dephosphorylation of rhodopsin can be controlled by the retina-associated protein kinase FA, representing an efficient cyclic cascade mechanism possibly involved in the rapid regulation of rhodopsin function in retina.

Adenosine Triphosphate↗
PubMed1991

Selective modulation of the two antagonistic activities of protein kinase FA (the activator of ATP.Mg-dependent protein phosphatase).

The ATP.Mg-dependent protein phosphatase activating factor (FA) has been identified as a protein kinase. The results are unexpected since factor FA possesses two activities which are antagonistic. As a kinase, factor FA catalyzes protein phosphorylation, while as a phosphatase activator, it catalyzes protein dephosphorylation. In this report, we found that the two opposing activities of factor FA could be selectively modulated. For instance, heparin at concentrations of 0.1-0.3 mg/ml could stimulate FA to work preferentially as a kinase towards phosphorylation of proteins but simultaneously inhibit it to work as a phosphatase activator towards dephosphorylation of the same proteins. In a similar manner, alkaline pH could stimulate FA to work as a kinase but block it to work as a phosphatase activator. This is the first report providing initial evidence that the two opposing activities of factor FA can be selectively modulated in a reciprocal manner by various triggers, suggesting that a simultaneous coordinate control mechanism may well be involved in regulating the activities of factor FA in the cell.

Adenosine Triphosphate↗
PubMed1991

Identification and characterization of the ATP.Mg-dependent protein phosphatase activator (FA) as a microtubule protein kinase in the brain.

The activating factor of ATP.Mg-dependent protein phosphatase (FA) has been identified in brain microtubules. When using purified MAP-2 (microtubule associated protein 2) and tau proteins as substrates, FA could phosphorylate MAP-2 to 16 moles of phosphates per mole of protein with a Km value of 0.4 microM, and tau proteins to 4 moles of phosphates per mole of proteins with a Km value of about 3 microM. When using microtubules as substrates, FA could enhance many-fold the endogenous phosphorylation of many microtubule-associated proteins including MAP-2, tau proteins, and several low-molecular-weight MAPs. In contrast to other reported MAP kinases, such as cAMP-dependent protein kinase and Ca+2/phospholipid-dependent protein kinase, the FA-catalyzed phosphorylation of tau proteins could cause an electrophoretic mobility shift on sodium dodecyl sulfate polyacrylamide gel electrophoresis, suggesting that a dramatic conformational change of tau proteins was produced by FA. Peptide mapping analysis of the phosphopeptides derived from SV8 protease digestion revealed that FA could phosphorylate MAP-2 and tau proteins on at least four specific sites distinctly different from those phosphorylated by cAMP-dependent and Ca+2/phospholipid-dependent MAP kinases. Quantitative analysis further indicated that approximately 19% of the total endogenous kinase activity in brain microtubules was due to FA. Taken together, the results provide initial evidence that the ATP.Mg-dependent protein phosphatase activating factor (FA) is a potent and unique MAP kinase, and may represent one of the major factors involved in phosphorylation of brain microtubules.

Adenosine Triphosphate↗
PubMed1990

Cyclic AMP induces activity increase of kinase FA (a transmembrane signal of insulin) during NG108-15 hybrid cell differentiation.

The ATP.Mg-dependent protein phosphatase activating factor (protein kinase FA) has been identified to exist in neuroblastoma x glioma hybrid 108-15 cells (NG108-15 cells). More importantly, when NG cells were induced to differentiate with N6, O2'-dibutyryl adenosine 3',5'-cyclic monophosphate (dibutyryl cAMP), the cellular activity of kinase FA was found to increase dramatically. Time course study further revealed that induction of differentiation in NG cells by dibutyryl cAMP treatment increased the FA activity to over 3 times the levels found in undifferentiated cells and in a linear day-dependent manner, indicating that the FA activity level is correlated with the state of differentiation of NG108-15 cells. This is the first report providing initial evidence that protein kinase FA (a transmembrane signal of insulin) is involved in the induction of neuronal cell differentiation.

Animals↗
PubMed1990

Regulation of protein kinase FA (a transmembrane signal of insulin and epidermal growth factor) in the brain.

Two forms of type-1 protein phosphatase activating factor (FA) termed FA1 and FA2 have been identified in plasma membranes of pig brain. FA1 is spontaneously active and trypsin-labile whereas FA2 is inactive and trypsin-resistant. Phospholipid reconstitution studies further indicate that the FA activity in the neutral phospholipids-reconstituted complex is spontaneously active and trypsin-labile whereas the FA activity in the acidic phospholipids-reconstituted complex is trypsin-resistant and inactive. The results indicate that inactive FA2 may have its catalytic domain interacted with negatively-charged phospholipids in brain membranes. This provides initial evidence for the regulation of protein kinase FA (a transmembrane signal of insulin and epidermal growth factor) in the central nervous system.

Animals↗
PubMed1990

On the mechanism of activation of protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase) in brain myelin.

Protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase) has been characterized to exist in two forms in the purified brain myelin. One form of kinase FA is spontaneously active and trypsin-labile, whereas the other form of kinase FA is inactive and trypsin-resistant, suggesting a different membrane topography with active FA exposed on the outer face of the myelin membrane and inactive FA buried within the myelin membrane. When myelin was solubilized in 1% Triton X-100, all kinase FA became active and trypsin-labile. Phospholipid reconstitution studies further indicated that when kinase FA was reconstituted in acidic phospholipids, such as phosphatidylinositol and phosphatidylserine, the enzyme activity was inhibited in a dose-dependent manner, suggesting that kinase FA interacts with acidic phospholipids which inhibit its activity. Furthermore, when myelin was incubated with exogenous phospholipase C, the inactive/trypsin-resistant FA could be converted to the active/trypsin-labile FA in a time- and dose-dependent manner. Taken together, it is concluded that membrane phospholipids play an important role in modulating the activity of kinase FA in the brain myelin. It is suggested that phospholipase C may mediate the activation-sequestration of inactive/trypsin-resistant kinase FA in the brain myelin through the phospholipase C-catalyzed degradation of acidic membrane phospholipids. The activation-sequestration of protein kinase FA may represent one mode of control modulating the activity of kinase FA in the central nervous system myelin.

Animals↗
PubMed1990

Selective activation of the two catalytic sites in the ATP.Mg-dependent phosphoprotein phosphatase by kinase Fa and Mn2+ ion.

1. Although Mn2+ could mimic kinase FA/ATP.Mg to activate ATP.Mg-dependent protein phosphatase, strong indications have been obtained that the Mn2(+)-activated and FA/ATP.Mg-activated phosphatase forms are not identical in terms of their substrate specificities and catalytic properties. 2. Both Mn2(+)-activated and FA/ATP.Mg-activated phosphatase forms readily dephosphorylate 32P-labeled phosphorylase a and myelin basic protein (MBP), however the Mn2(+)-activated phosphatase displays activity preferentially against [32P]MBP and FA/ATP.Mg-activated phosphatase preferentially dephosphorylates [32P]phosphorylase a, representing a unique control mechanism to regulate the substrate specificity of multisubstrate protein phosphatase in mammalian tissues.

Adenosine Triphosphate↗
PubMed1989

Epidermal growth factor induces activation of protein kinase FA and ATP.Mg-dependent protein phosphatase in A431 cells.

The cytosolic fractions from epidermal growth factor (EGF)-treated A431 cells exhibit a marked increase in activities of ATP.Mg-dependent protein phosphatase and its activating factor (protein kinase FA) when compared to controls in the absence of EGF. By contrast, the Triton X-100-solubilized membrane fractions from the same EGF-treated cells exhibit a corresponding decrease in protein kinase FA activity. The EGF-dependent activation of protein kinase FA and ATP.Mg-dependent protein phosphatase occurred within physiological concentrations of EGF (ED50 = 5 x 10(-10) M). The changes of kinase and phosphatase activities which were measured concomitantly exhibit very similar characteristics as to EGF sensitivity and time dependence. The EGF-induced kinase and phosphatase activation occurred very rapidly, reaching the maximal activity levels within 3 min. Moreover, the EGF effect is transient; both EGF-stimulated phosphatase and kinase activities returned to control levels within 30 min. Taken together, the results suggest that EGF may induce the activation of kinase FA in the membrane and thereby promotes the activation of ATP.Mg-dependent phosphatase in the cytosol. Exposure of A431 cells to exogenous phospholipase C also resulted in the activation of endogenous kinase FA and ATP.Mg-dependent phosphatase in a similar pattern produced by EGF. This further suggests that phospholipase C can mimic EGF to mediate the activation of kinase FA and ATP.Mg-dependent phosphatase in A431 cells. By its dual role as a multisubstrate protein kinase and as an activating factor of multisubstrate protein phosphatase, protein kinase FA may represent a transmembrane signal of EGF.

Adenosine Triphosphate↗
PubMed1989

Insulin induces activation of kinase FA in membranes and thereby promotes activation of ATP.Mg-dependent phosphatase in adipocytes.

Exposure of rat adipocytes to physiological concentrations of insulin resulted in a time- and concentration-dependent activation-translocation of kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase) in plasma membranes and the subsequent activation of ATP.Mg-dependent protein phosphatase in the cytosol. The insulin-induced activation of membrane-associated kinase FA and cytosolic ATP.Mg-dependent protein phosphatase occurred very rapidly, reaching the maximal activity levels within 3 min. Moreover, the insulin effect is transient; the insulin-stimulated FA activity in membranes and ATP.Mg-dependent phosphatase activity in the cytosol returned to control levels within 30 min. It is concluded that insulin may induce the activation of kinase FA in membranes and thereby promotes the activation of ATP.Mg-dependent multifunctional protein phosphatase in the cytosol of rat adipocytes in order to mediate some of its intracellular effects through the dephosphorylation reactions. The release of factor FA from plasma membranes may represent one of the transmembrane signalling mechanisms for insulin actions.

Adenosine Triphosphate↗
PubMed1989

Purification and characterization of a Mn2+/phospholipid-dependent protein phosphatase from pig brain membranes.

A Mn2+/phospholipid-dependent protein phosphatase has been identified and characterized from brain membranes. The phosphatase contains three subunits with molecular weights of 64,000, 54,000, and 35,000 in a 1:1:1 molar ratio. On gel filtration, the enzyme has an apparent molecular weight of approximately 180,000. The phosphatase was active on many substrates, including p-nitrophenyl phosphate, phosphotyrosine, phosphothreonine, phosphorylase a, myelin basic protein, histones, type 1 phosphatase inhibitor-2, microtubule tau protein, and synapsin I. To dephosphorylate phosphoproteins, the phosphatase was dependent on such acidic phospholipids as phosphatidylinositol and phosphatidylserine but not on neutral phospholipids such as phosphatidylcholine and phosphatidylethanolamine. The phospholipid-mediated activation of the phosphatase was time and dose dependent and could be reversed by Triton X-100 or gel filtration. Kinetic study further indicates that phospholipid was able to increase the Vmax of the phosphatase but had no effect on the Km value for substrates, suggesting a direct interaction of phospholipids with the phosphatase. Conversely, in order to dephosphorylate phosphoamino acids such as phosphotyrosine and phosphothreonine, this phosphatase was entirely dependent on Mn2+. Phospholipids had no effect on the dephosphorylation of phosphoamino acids, whereas Mn2+ had no effect on the dephosphorylation of phosphoproteins. It is concluded that this Mn2+/phospholipid-dependent membrane phosphatase has two distinct activation mechanisms. The enzyme requires Mn2+ to dephosphorylate micromolecules, whereas acidic phospholipids are needed to dephosphorylate macromolecules. This suggests that Mn2+ and phospholipids may play a role in regulating the substrate specificity of this multisubstrate membrane phosphatase.

Animals↗
PubMed1989

[Case report of orthodontic approach to temporomandibular disorders].

The purpose of the present article is to describe a case in which malocclusion patient accompanied with temporomandibular disorders was treated with the fixed appliance and Gnathological Tooth Positioner. Patient, a girl aged 16 years 9 months, had a skeletal Class III malocclusion with mandibular protrusion and anterior edge to edge bite. Centric Relation Splint was made to alleviate the acute symptoms and Gnathological Tooth positioner at the finishing stage of fixed appliance was applied to achieve the functional occlusion. After 12 months of active treatment, the patient gained a normal overbite-overjet relationship. Observation after 2 years out of retention revealed a stable occlusion.

Adolescent↗
PubMed1988

Dephosphorylation of the beta 2-adrenergic receptor and rhodopsin by latent phosphatase 2.

Recent evidence suggests that the function of receptors coupled to guanine nucleotide regulatory proteins may be controlled by highly specific protein kinases, e.g. rhodopsin kinase and the beta-adrenergic receptor kinase. In order to investigate the nature of the phosphatases which might be involved in controlling the state of receptor phosphorylation we studied the ability of four highly purified well characterized protein phosphatases to dephosphorylate preparations of rhodopsin or beta 2-adrenergic receptor which had been highly phosphorylated by beta-adrenergic receptor kinase. These included: type 1 phosphatase, calcineurin phosphatase, type 2A phosphatase, and the high molecular weight latent phosphatase 2. Under conditions in which all the phosphatases could dephosphorylate such common substrates as [32P]phosphorylase a and [32P]myelin basic protein at similar rates only the latent phosphatase 2 was active on the phosphorylated receptors. Moreover, a latent phosphatase activity was found predominantly in a sequestered membrane fraction of frog erythrocytes. This parallels the distribution of a beta-adrenergic receptor phosphatase activity recently described in these cells (Sibley, D. R., Strasser, R. H., Benovic, J. L., Daniel, K., and Lefkowitz, R. J. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 9408-9412). These data suggest a potential role for the latent phosphatase 2 as a specific receptor phosphatase.

Animals↗
PubMed1988

Insulin induces activation and translocation of protein kinase FA (a multifunctional protein phosphatase activator) in human platelet.

Protein kinase FA (an activator of the ATP.Mg-dependent multifunctional protein phosphatase) has been identified in both cytosol and plasma membrane isolated from human platelets. The FA activity in the cytosol is active whereas the FA activity in the membrane is inactive. Quantitative analysis further indicates that approximately 90% of total FA is present in the membrane whereas only 10% of FA is localized in the cytosol, suggesting that the inactive membrane-associated FA might be regulated. This notion has subsequently been demonstrated that exposure of platelets to physiological concentrations of insulin for only 1 min resulted in an increase in cytosolic FA activity to about 300% of control values in the absence of insulin and in a corresponding decrease in FA activity in the membrane. It is concluded that the molecular basis for insulin action on cellular metabolism may partly be mediated through the activation and translocation of protein kinase FA in the membrane. It is suggested that redistribution of protein kinase FA may represent a transmembrane signal of insulin.

Animals↗