pp60c-src Increases Voltage-Operated Calcium Channel Currents in Vascular Smooth Muscle Cells

Wijetunge, S; Hughes, Alun D.

doi:10.1006/bbrc.1995.2874

Cited by 74 publications

(51 citation statements)

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“…Src has been shown to alter the function of a number of ion channels, including inhibition of delayed rectifier K ϩ currents (Holmes et al, 1996;MacFarlane and Sontheimer, 2000;Nitabach et al, 2001Nitabach et al, , 2002, and enhancement of NMDA receptors (Wang and Salter, 1994;Yu et al, 1997), the cystic fibrosis Cl Ϫ channel (Fischer and Machen, 1996), and voltage-gated Ca 2ϩ currents (Wijetunge and Hughes, 1995). In the present study, we found that exogenously applied Src significantly reduced cation channel P O , and this could be prevented by the Src-family tyrosine kinase inhibitor PP1.…”

Section: Discussionsupporting

confidence: 56%

Association/Dissociation of a Channel–Kinase Complex Underlies State-Dependent Modulation

Magoski¹,

Kaczmarek²

2005

J. Neurosci.

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Although ion channels are regulated by protein kinases, it has yet to be established whether the behavioral state of an animal may dictate whether or not modulation by a kinase can occur. Here, we describe behaviorally relevant changes in the ability of a nonselective cation channel from Aplysia bag cell neurons to be regulated by protein kinase C (PKC). This channel drives a prolonged afterdischarge that triggers the release of egg-laying hormone and a series of reproductive behaviors. The afterdischarge is followed by a lengthy refractory period, during which additional bursting cannot be elicited. Previously, we reported that, in excised inside-out patches, the cation channel is closely associated with PKC, which increases channel activity. We now show that this channel-kinase association is plastic, because channels excised from certain neurons lack PKC-dependent modulation. Although direct application of PKC-activating phorbol ester to these patches had no effect, exposing the neurons themselves to phorbol ester reinstated modulation, suggesting that an absence of modulation was attributable to a lack of associated kinase. Furthermore, modulation was restored by pretreating neurons with either PP1 [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] or SU6656, inhibitors of Src tyrosine kinase, an enzyme whoseSrc homology 3 domain is required for channel-PKC association. Neurons that were stimulated to afterdischarge and had entered the prolonged refractory period were found to have more phosphotyrosine staining and less channel-PKC association than unstimulated neurons. These findings suggest that Src-dependent regulation of the association between the cation channel and PKC controls both the long-term excitability of these neurons and their ability to induce reproduction.

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Section: Discussionsupporting

confidence: 56%

Association/Dissociation of a Channel–Kinase Complex Underlies State-Dependent Modulation

Magoski¹,

Kaczmarek²

2005

J. Neurosci.

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“…Phosphorylation of the Torpedo AChR by the SFKs, Fyk, and Fyn was found to modulate synaptic transmission at the neuromuscular junction (15), and microinjection of isolated c-Src into vascular smooth muscle cells resulted in increased voltage-operated calcium channel currents that were dependent on c-Src kinase activity (60). c-Src was also found to be associated with the tyrosine-phosphorylated ␥2 subunit of GABA receptor which may regulate the function of this receptor in brain (20) Likewise, c-Src was capable of phosphorylating the Kv1.5 potassium channel, resulting in modulation of the potassium currents of this channel and regulation of astrocyte differentiation (61).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Neuronal Nicotinic Acetylcholine Receptor by Src Family Tyrosine Kinases

Wang¹,

Hackett

Cox³

et al. 2004

Journal of Biological Chemistry

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“…To investigate the role of tyrosine phosphorylation in neurotransmitter release, first we tested the effect of genistein, a nonselective tyrosine kinase inhibitor, on Ca 2ϩ -dependent dopamine release from clonal rat pheochromocytoma PC12 cells. We induced Ca 2ϩ channel-independent Ca 2ϩ influx with a Ca 2ϩ ionophore, ionomycin, to evoke Ca 2ϩ -dependent dopamine release because some kinase inhibitors were reported to affect ion channel activities (15)(16)(17). Pretreatment of the cells with 50 M genistein for 20 min caused a marked enhancement of dopamine release evoked by ionomycin from PC12 cells (Fig.…”

Section: Enhancement Of Dopamine Release From Pc12 Cells By Tyrosine mentioning

confidence: 99%

A src family tyrosine kinase inhibits neurotransmitter release from neuronal cells

Ohnishi

Yamamori²,

Ono³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Tyrosine kinases are expressed in many tissues, particularly in the central nervous system, and regulate various cellular functions. We report here that a src family tyrosine kinase-specific inhibitor, PP2, enhances neurotransmitter release from PC12 cells and primary cultured neurons. PP2 enhances only Ca 2؉ -dependent release; it does not affect basal release. These effects result from an enhancement of vesicular exocytosis and not from the reuptake or refilling of neurotransmitters because Ca 2؉ -dependent secretion of an exogenously expressed reporter protein, the human growth hormone (hGH), is also enhanced by PP2. Overexpression of constitutive active v-src, but not of a kinase-inactive mutant, suppressed Ca 2؉ -dependent release. In PP2-treated cells, Pyk2, paxillin, and some other proteins showed a decrease in tyrosine phosphorylation, and the enhancement of tyrosine phosphorylation of these proteins in response to Ca 2؉ influx was also reduced. Electron and fluorescence microscopy showed that PP2 treatment induced morphological change and decreased phalloidin reactivity at the filopodium-like structures on the processes of PC12 cells. Interestingly, inhibition of actin polymerization with cytochalasin D and latrunculin A enhanced Ca 2؉ -dependent, but not basal, release. It is possible that a src family tyrosine kinase, through the regulation of actin dynamics, has an inhibitory function to regulate neurotransmitter release.N eurotransmitters are accumulated in synaptic vesicles in presynaptic nerve terminals. Ca 2ϩ influx through voltagegated Ca 2ϩ channels triggers the release of neurotransmitters into the synaptic cleft by means of an exocytosis of synaptic vesicles. The modulation of neurotransmitter release is one of the cellular mechanisms for the regulation of synaptic transmission, and the involvement of various kinases has been suggested (1). Tyrosine kinases are classified as receptor types or nonreceptor types, both of which are abundant in the central nervous system. The receptor-type tyrosine kinase generally acts as a receptor for growth and trophic factors and plays an important role in the regulation of synaptic transmission through the up-regulation of neurotransmitter release from synapses of developing and mature neurons (2). The nonreceptor-type tyrosine kinase is well documented to have postsynaptic functions and is shown to phosphorylate neurotransmitter receptors, including nicotinic acetylcholine receptor (nACh-R), N-methyl-D-aspartate receptor (NMDA-R), and ␥-aminobutyric acid type A receptor (GABA A -R) (3). src kinase, a nonreceptor tyrosine kinase expressed in the central nervous system, is accumulated in synaptic vesicles and accounts for the majority of synapticvesicle tyrosine kinase activity (4, 5). Ca 2ϩ influx, which triggers neurotransmitter release, activates src kinase and induces tyrosine phosphorylation of several proteins, including synaptophysin, a synaptic vesicle protein (6-8). On synaptic vesicles, c-src interacts with synapsin, a perimembrane protein on these...

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pp60c-src Increases Voltage-Operated Calcium Channel Currents in Vascular Smooth Muscle Cells

Cited by 74 publications

References 0 publications

Association/Dissociation of a Channel–Kinase Complex Underlies State-Dependent Modulation

Association/Dissociation of a Channel–Kinase Complex Underlies State-Dependent Modulation

Regulation of the Neuronal Nicotinic Acetylcholine Receptor by Src Family Tyrosine Kinases

A src family tyrosine kinase inhibits neurotransmitter release from neuronal cells

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