Protein kinase C in the regulation of smooth muscle contraction

Rasmussen, Howard; Takuwa, Yoh; Park, Susanna

doi:10.1096/fasebj.1.3.3040504

Cited by 521 publications

(197 citation statements)

References 31 publications

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“…Activated PKC can phosphorylate a number of contractile, cytoskeletal and ion channel/ antiporter proteins any or all of which may lead to the increase in isometric tension that is observed in PDButreated vascular muscle [28]. PKC could also activate other protein kinase systems through a phosphorylation cascade or via changes in intraeellular Ca '-+.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation sequences in h‐caldesmon from phorbol ester‐stimulated canine aortas

1992

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The high molecular weight form of caldesmon (h‐caldesmon) is phosphorylated in vascular smooth muscle. The stoichiometry of caldesmon phosphorylation increases in response to stimulation of the muscle by several contractile agonists; however, the responsible kinase has not been identified. In this study, we have sequenced the phosphopeptides prepared from h‐caldesmon phosphorylated in vitro by protein kinase C (PKC) as well as the phosphopeptides prepared from caldesmon phosphorylated in intact canine aortas that were stimulated to contract with PDBu. PKC phosphorylated three sites located in the C terminus: GSS*LKIEE, AEFLNKS*VQK and NLWEKQS*VDK, while h‐caldesmon from intact tissue was phosphorylated at two separate sites also in the C terminus: VTS*PTKV and S*PAPK. By comparison to known substrate consensus sequences for various protein kinases these data suggest that h‐caldesmon is directly phosphorylated by a proline‐directed protein kinase and not by PKC.

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Section: Discussionmentioning

confidence: 99%

Phosphorylation sequences in h‐caldesmon from phorbol ester‐stimulated canine aortas

1992

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“…The phosphorylation of these proteins appears to occur as a direct or indirect consequence of the activation of PKC [17]. The temporal change in the pattern of phosphoproteins and the distinct effects ofphorbol esters on smooth muscle contraction [12][13][14] have led to the proposal that the initial and sustained phases of smooth muscle contraction are mediated by different cellular and molecular events [17].…”

Section: Introductionmentioning

confidence: 99%

“…During this latter phase, it has been proposed that the activation of membrane-associated PKC by altered Ca2+ influx leads directly or indirectly to the phosphorylation of a number of cytosolic proteins as well as fibrillar proteins such as desmin and caldesmon [8,16,18]. It is postulated that these late-phase phosphoproteins are involved in tension maintenance [17,19]. In view of the recent studies by Marston and colleagues [20] showing that caldesmon interacts with actin, and those of Adam et al [18] showing agonist-and phorbol ester-dependent phosphorylation of caldesmon, it is possible that the phosphorylation of caldesmon may play a role in maintaining smooth muscle contraction.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase C translocation in intact vascular smooth muscle strips

Haller

Smallwood

Rasmussen

1990

Biochemical Journal

108

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Using intact muscle strips from the bovine carotid artery, the time course of translc~ation of protein kinase C (PKC) from the cytosol to the membrane fraction was measured in response to various agonists at induce contractile responses. PKC activity was assessed by Ca2+/phospholipid-dependent phosphorylation of histoiie. Exposure of the muscle strips to phorbol ester (12-deoxyphorbol 1 3-isobutyrate) induced a rapid and sustained translocation of PKC from the cytosol to the membrane fraction, and a slowly developing but sustained contractile response. Histamine induced a comparable initial translocation of PKC to the membrane which then decreased somewhat to a stable plateau significantly above basal values. Histamine also led to a rapid and sustained increase in tension. Angiotensin I, which caused a rapid but transient contraction, induced a rapid initial translocation of PKC to the membrane. The men. brane-associated PKC then declined to a stable plateau significantly lower than that seen after a histamine-induced respon.e, and only slightly above the basal value. Endothelin, which induced a sustained contraction, caused a sustained translocation of PKC from the cytosol to the membrane. In contrast, although exposure to 35 mM-KCI induced a rapid and sustained contraction, it caused only a transient translocation of PKC; the membrane-associated PKC returned to its basal value within 20 min. These results demonstrate that PKC in intact smooth muscle can be rapidly translocated to the membrane and remains membranebound during sustained phorbol ester-or agonist-induced contractions, but that such .t sustained translocation of PKC does not occur during prolonged stimulation with KCI. INTRODUCTIONThe Ca2+/phospholipid-dependent protein kinase, protein kinase C (PKC), is widely distributed in tissues and organs [1]. Over the last few years the enzyme has been implicated in the regulation of an increasing number of cellular processes [1][2][3][4]. In vascular smooth muscle, PKC is present in relatively high concentrations [4], suggesting that it also plays an important role in the control of smooth muscle function. A unique feature of PKC regulation is the spatial translocation of the enzyme. Under basal conditions PKC is thought to be located mainly in the cytosol, but after hormonal stimulation PKC is rapidly translocated to the membrane where it associates with membrane phospholipids [4]. The activation of the enzyme is often closely linked to changes in phosphoinositide (PI) metabolism [3]. When an appropriate agonist activates a specific receptor, an immediate receptor-linked event is the activation of a specific phospholipase C that catalyses the rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to two intracellular messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) [2]. It has been shown that IP3 triggers the release of Ca2+ from intracellular stores in smooth-muscle [5]. Likewise, it has been demonstrated that appropriate agonists induce sustained increases in the DAG cont...

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“…To explain the force main tenance during the sustained phase of smooth mus cle contraction, the occurrence of a "latch mechanism" in the myosin-actin interaction has been proposed (Aksoy et aI., 1982(Aksoy et aI., , 1983, In keep ing with this line of thinking, Rasmussen et al (1987) advocated that the sustained smooth muscle contraction is due to phosphorylation of proteins other than myosin light chain by protein kinase C (PKC). This thesis has been supported by numerous succeeding reports, using a variety of arterial smooth muscles (Danthuluri and Deth, 1984;Bara van et ai.…”

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confidence: 99%

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Matsui¹,

Takuwa

Johshita³

et al. 1991

J Cereb Blood Flow Metab

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Summary:In the present study, we investigate the pos sible role of protein kinase C (PKC)-dependent smooth muscle contraction in cerebral vasospasm following sub arachnoid hemorrhage (SAH), employing the beagle "two-hemorrhage" model. The occurrence of chronic va sospasm was angiographically confirmed on day 7 in the basilar artery, which was exposed via the transclival ap proach. The artery was superfused with aerated Krebs Henseleit solution containing various agents, and the sub sequent changes in the basilar artery diameter were re corded by successive angiography. The preexisting spasm was not ameliorated by local application of neuro transmitter antagonists (atropine, methysergide, phentol amine, and diphenhydramine), calmodulin inhibitors (R24571 and W-7), or a calcium antagonist, nicardipine. However, the application of PKC inhibitors such as H-7 and staurosporine induced significant dilation of the ar tery. In another experiment, an intrinsic PKC activator,The refractoriness of chronic vasospasm to va sodilator therapy has been well documented (Bevan and Bevan, 1988). Particularly, the Ca2+ -antagonist nimodipine, administered via various routes, has in variably failed to reverse chronic vasospasm (Espi nosa et aI. , 1984; Grotenhuis et aI., 1984; Nosko et aI., 1985; Lewis et aI., 1988). Since agonist-induced smooth muscle contraction has been thought to be dependent on intracellular influx of external Ca2+, Received December 28, 1989; revised July 23, 1990; accepted July 24, 1990. 1431,2-diacylglycerol (DAG), in the basilar artery, the CSF, and the cisternal clot of beagles exposed to two hemor rhages was measured on days 1, 2,4,7, and 14 using the DAG kinase method. On days 2, 4, and 7, the DAG con tent of the basilar artery showed a significant and pro longed increase (150-190% of control), whereas it was unchanged on days I and 14. Throughout the experimen tal period, there was a significant linear correlation be tween the DAG content and the angiographical diameter of the basilar artery. The above results indicate that SAH leads to an increase in the DAG level within the cerebral artery through an as yet unknown mechanism and that subsequent activation of the PKC-dependent contractile system participates in the occurrence of chronic vaso spasm. Key Words: Cerebral vasospasm-l,2-Diac ylglycerol-H-7-Protein kinase C-Vascular smooth muscle.it has been conjectured that the primary cause of chronic vasospasm might be the changes in the physical properties in the arterial wall rather than active smooth muscle contraction (Bevan and Be van, 1988; Findlay et aI., 1989; Kim et aI., 1989).However, it has recently been shown that during the sustained phase of agonist-induced smooth mus cle contraction, neither the intracellular concentra tion of Ca2+ nor the phosphorylation of myosin light chain is increased (DeFeo and Morgan, 1985;Kamm and Stull, 1985). To explain the force main tenance during the sustained phase of smooth mus cle contraction, the occurrence of a "latch mechanism" in the myosin-actin i...

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Protein kinase C in the regulation of smooth muscle contraction

Cited by 521 publications

References 31 publications

Phosphorylation sequences in h‐caldesmon from phorbol ester‐stimulated canine aortas

Phosphorylation sequences in h‐caldesmon from phorbol ester‐stimulated canine aortas

Protein kinase C translocation in intact vascular smooth muscle strips

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

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