scholarly journals Protein phosphatase-1M and Rho-kinase affect exocytosis from cortical synaptosomes and influence neurotransmission at a glutamatergic giant synapse of the rat auditory system

2012 ◽  
Vol 123 (1) ◽  
pp. 84-99 ◽  
Author(s):  
Beáta Lontay ◽  
Balázs Pál ◽  
Zoltán Serfőző ◽  
Áron Kőszeghy ◽  
Géza Szücs ◽  
...  
Keyword(s):  
Auditory System ◽  
Protein Phosphatase ◽  
Rho Kinase ◽  
Giant Synapse

scholarly journals Regulation of Myosin Phosphatase Through Phosphorylation of the Myosin-Binding Subunit in Platelet Activation

Blood ◽  
1997 ◽  
Vol 90 (10) ◽  
pp. 3936-3942 ◽  
Author(s):  
Keiji Nakai ◽  
Yoshinori Suzuki ◽  
Hisakazu Kihira ◽  
Hideo Wada ◽  
Masanori Fujioka ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Rho Kinase ◽  
Human Platelets ◽  
Myosin Phosphatase ◽  
Phosphatase Treatment ◽  
Myosin Binding ◽  
Muscle Myosin ◽  
Protein Phosphatase Type ◽  
Putative Mechanism ◽  
Binding Subunit

Abstract Human platelets were found to contain myosin phosphatase consisting of a 38-kD catalytic subunit of protein phosphatase type 1δ, a 130-kD myosin-binding subunit (MBS) and a 20-kD subunit, all of which cross-reacted with antibodies against these subunits of smooth muscle myosin phosphatase. Anti-MBS antibody coimmunoprecipitated RhoA and Rho-kinase of human platelets. Platelets MBS is a substrate for Rho-kinase and phosphorylation of MBS decreases the activity of myosin phosphatase. Treatment of intact platelets with 9,11-epithio-11,12-methano-thromboxane A2 led to a dramatic increase in phosphorylation of MBS and a significant decrease in the activity of myosin phosphatase. These findings suggest a putative mechanism for agonist-induced regulation of myosin phosphatase activity in platelets.

scholarly journals Hypertonic Stress Increases Phosphatidylinositol 4,5-Bisphosphate Levels by Activating PIP5KIβ

2006 ◽  
Vol 281 (43) ◽  
pp. 32630-32638 ◽  
Author(s):  
Masaya Yamamoto ◽  
Mark Z. Chen ◽  
Ying-Jie Wang ◽  
Hui-Qiao Sun ◽  
Yongjie Wei ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Protein Phosphatase ◽  
Rho Kinase ◽  
Type I ◽  
Dependent Manner ◽  
Calyculin A ◽  
Lipid Kinase ◽  
Kinase Activation ◽  
Hypertonic Stress ◽  
In Cells

Hyperosmotic stress increases phosphoinositide levels, reorganizes the actin cytoskeleton, and induces multiple acute and adaptive physiological responses. Here we showed that phosphatidylinositol 4,5-bisphosphate (PIP2) level increased rapidly in HeLa cells during hypertonic treatment. Depletion of the human type I phosphatidylinositol 4-phosphate 5-kinase β isoform (PIP5KIβ) by RNA interference impaired both the PIP2 and actin cytoskeletal responses. PIP5KIβ was recruited to membranes and was activated by hypertonic stress through Ser/Thr dephosphorylation. Calyculin A, a protein phosphatase 1 inhibitor, blocked the hypertonicity-induced PIP5KIβ dephosphorylation/activation as well as PIP2 increase in cells. Urea, which raises osmolarity without inducing cell shrinkage, did not promote dephosphorylation nor increase PIP2 levels. Disruption or stabilization of the actin cytoskeleton, or inhibition of the Rho kinase, did not block the PIP2 increase nor PIP5KIβ dephosphorylation. Therefore, PIP5KIβ is dephosphorylated in a volume-dependent manner by a calyculin A-sensitive protein phosphatase, which is activated upstream of actin remodeling and independently of Rho kinase activation. Our results establish a cause-and-effect relation between PIP5KIβ dephosphorylation, lipid kinase activation, and PIP2 increase in cells. This PIP2 increase can orchestrate multiple downstream responses, including the reorganization of the actin cytoskeleton.

Modulation of myosin phosphatase targeting subunit and protein phosphatase 1 in the heart

2005 ◽  
Vol 289 (4) ◽  
pp. H1736-H1743 ◽  
Author(s):  
Ravi Rajashree ◽  
Bradford C. Blunt ◽  
Polly A. Hofmann
Keyword(s):  
Protein Phosphatase ◽  
Adrenergic Receptor ◽  
Ventricular Myocytes ◽  
Regional Distribution ◽  
Rho Kinase ◽  
Receptor Activation ◽  
Spatial Gradient ◽  
Receptor Stimulation ◽  
Adult Rat ◽  
Myosin Light Chain 2

Myosin light chain 2 (LC2) phosphorylation is of both physiological and pathological importance to myocardial function. The phosphatase that directly dephosphorylates LC2 is a type 1 protein phosphatase (PP1) that contains a catalytic subunit that complexes with a myosin-binding phosphatase targeting subunit (MYPT). The goal of the present study was to examine the role of MYPT in the regulation of PP1 in ventricular myocytes. In the first part of the study, regional distribution of MYPT expression and phosphorylation were determined in unstimulated hearts. The pattern of MYPT phosphorylation was inversely related to the LC2 phosphorylation spatial gradient as described by Epstein and colleagues (Davis JS, Hassanzadeh S, Winitsky S, Lin H, Satorius C, Vemuri R, Aletras AH, Wen H, and Epstein ND. Cell 107: 631–641, 2001). In the second part of the study, adult rat isolated ventricular myocytes were exposed to an α-adrenergic receptor agonist, and properties of MYPT, PP1, and LC2 were studied. We found MYPT associates with cardiac myofilaments, and this association increases upon α-adrenergic receptor stimulation. Activation of α-adrenergic receptors also led to a decrease in the PP1-myofilament association. Furthermore, α-adrenergic receptor stimulation results in phosphorylation of MYPT and LC2 and an increase in myocyte Ca2+ sensitivity of tension that all depend on Rho kinase activation. These data support the hypothesis that α-adrenergic receptor activation works through Rho kinase to phosphorylate MYPT, and phosphorylated MYPT dissociates from PP1 so that PP1 is no longer physically associated with LC2. Hence, we propose a pathway for the dynamic modulation of LC2 phosphorylation through receptor-dependent phosphorylation of MYPT, and a spatial gradient of LC2 phosphorylation under basal conditions that occurs due to varied levels of phosphorylation of MYPT in ventricles.

Differential participation of protein kinase C and Rho kinase in α1-adrenoceptor mediated contraction in rat arteries

2004 ◽  
Vol 82 (10) ◽  
pp. 895-902 ◽  
Author(s):  
Irem Mueed ◽  
Perminder Bains ◽  
Lili Zhang ◽  
Kathleen M MacLeod
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Phosphatase ◽  
Rho Kinase ◽  
Rat Aorta ◽  
Contractile Responses ◽  
Kinase C ◽  
Caudal Artery ◽  
Adrenoceptor Agonist ◽  
Stimulation Of

The major functional α1-adrenoceptor in the rat aorta is of the α1Dsubtype and that in the caudal artery is of the α1Asubtype. In the present study, the participation of protein kinase C (PKC) and Rho kinase (RhoK) in contractile responses to stimulation of the α1-adrenoceptors in these two arteries was investigated. Both the PKC inhibitor Ro-318220 and the RhoK inhibitor Y-27632 significantly blocked contractile responses of the aorta to phenylephrine (PE) and the selective α1A-adrenoceptor agonist A61603. When used in combination, the inhibitors had an additive blocking effect. In the caudal artery, Y-27632 but not Ro-318220 inhibited contractile responses to PE and A61603, and, in combination, the antagonism produced was no greater than that by Y-27632 alone. Contractile responses to direct activation of PKC with phorbol 12,13-dibutyrate were much smaller and levels of CPI-17 (PKC-activated protein phosphatase inhibitor of 17 kDa) were much lower in the caudal artery than the aorta. The results suggest that both PKC and RhoK contribute independently to contractile responses to stimulation of α1D-adrenoceptors in the aorta. However, RhoK, but not PKC, participates in contractile responses to stimulation of α1A-adrenoceptors in the caudal artery. This difference may largely be due to differences between the two arteries in the extent to which PKC participates in contraction.Key words: vascular smooth muscle, α1-adrenoceptors, protein kinase C, rho kinase, phenylephrine.

scholarly journals Balance between Activities of Rho Kinase and Type 1 Protein Phosphatase Modulates Turnover of Phosphorylation and Dynamics of Desmin/Vimentin Filaments

1999 ◽  
Vol 274 (49) ◽  
pp. 34932-34939 ◽  
Author(s):  
Hiroyasu Inada ◽  
Hideaki Togashi ◽  
Yu Nakamura ◽  
Kozo Kaibuchi ◽  
Koh-ichi Nagata ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Rho Kinase ◽  
Vimentin Filaments

scholarly journals Regulation of Myosin-Bound Protein Phosphatase by Insulin in Vascular Smooth Muscle Cells: Evaluation of the Role of Rho Kinase and Phosphatidylinositol-3-Kinase-Dependent Signaling Pathways

2000 ◽  
Vol 14 (9) ◽  
pp. 1365-1376 ◽  
Author(s):  
Najma Begum ◽  
Noreen Duddy ◽  
Oana Sandu ◽  
Jennifer Reinzie ◽  
Louis Ragolia
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Protein Phosphatase ◽  
Rho Kinase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Regulatory Subunit ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

Abstract In this study, we examined the molecular mechanism of myosin-bound protein phosphatase (MBP) regulation by insulin and evaluated the role of MBP in insulin-mediated vasorelaxation. Insulin rapidly stimulated MBP in confluent primary vascular smooth muscle cell (VSMC) cultures. In contrast, VSMCs isolated from diabetic and hypertensive rats exhibited impaired MBP activation by insulin. Insulin-mediated MBP activation was accompanied by a rapid time-dependent reduction in the phosphorylation state of the myosin-bound regulatory subunit (MBS) of MBP. The decrease observed in MBS phosphorylation was due to insulin-induced inhibition of Rho kinase activity. Insulin also prevented a thrombin-mediated increase in Rho kinase activation and abolished the thrombin-induced increase in MBS phosphorylation and MBP inactivation. These data are consistent with the notion that insulin inactivates Rho kinase and decreases MBS phosphorylation to activate MBP in VSMCs. Furthermore, treatment with synthetic inhibitors of phosphatidylinositol-3 kinase (PI3kinase), nitric oxide synthase (NOS), and cyclic guanosine monophosphate (cGMP) all blocked insulin’s effect on MBP activation. We conclude that insulin stimulates MBP via its regulatory subunit, MBS partly by inactivating Rho kinase and stimulating NO/cGMP signaling via PI3-kinase as part of a complex signaling network that controls 20-kDa myosin light chain (MLC20) phosphorylation and VSMC contraction.

Evaluation of Efferent Auditory System and Hearing Quality in Parkinson's Disease: Is the Difficulty in Speech Understanding in Complex Listening Conditions Related to Neural Degeneration or Aging?

2020 ◽  
pp. 1-9
Author(s):  
Nuriye Yıldırım Gökay ◽  
Bülent Gündüz ◽  
Fatih Söke ◽  
Recep Karamert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Auditory System ◽  
Otoacoustic Emissions ◽  
Pure Tone ◽  
Pure Tone Audiometry ◽  
Auditory Pathway ◽  
Normal Hearing ◽  
System Function ◽  
Distortion Product

Purpose The effects of neurological diseases on the auditory system have been a notable issue for investigators because the auditory pathway is closely associated with neural systems. The purposes of this study are to evaluate the efferent auditory system function and hearing quality in Parkinson's disease (PD) and to compare the findings with age-matched individuals without PD to present a perspective on aging. Method The study included 35 individuals with PD (mean age of 48.50 ± 8.00 years) and 35 normal-hearing peers (mean age of 49 ± 10 years). The following tests were administered for all participants: the first section of the Speech, Spatial and Qualities of Hearing Scale; pure-tone audiometry, speech audiometry, tympanometry, and acoustic reflexes; and distortion product otoacoustic emissions (DPOAEs) and contralateral suppression of DPOAEs. SPSS Version 25 was used for statistical analyses, and values of p < .05 were considered statistically significant. Results There were no statistically significant differences in the pure-tone audiometry thresholds and DPOAE responses between the individuals with PD and their normal-hearing peers ( p = .732). However, statistically significant differences were found between the groups in suppression levels of DPOAEs and hearing quality ( p < .05). In addition, a statistically significant and positive correlation was found between the amount of suppression at some frequencies and the Speech, Spatial and Qualities of Hearing Scale scores. Conclusions This study indicates that medial olivocochlear efferent system function and the hearing quality of individuals with PD were affected adversely due to the results of PD pathophysiology on the hearing system. For optimal intervention and follow-up, tasks related to hearing quality in daily life can also be added to therapies for PD.

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