Ser1928 Is a Common Site for Cav1.2 Phosphorylation by Protein Kinase C Isoforms

Yang, Lin; Liu, Guoxia; Zakharov, Sergey I.; Morrow, John; Rybin, Vitalyi O.; Steinberg, Susan F.; Marx, Steven O.

doi:10.1074/jbc.m410509200

Cited by 104 publications

(113 citation statements)

References 61 publications

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“…This PKCregulated LVGC activity is thought to control the steady-state [Ca 2+ ] i in these SMCs. Finally, LVGCs form molecular association with several PKC isoforms in cardiac myocytes, and channel activation may occur as a result of phosphorylation of a serine residue at the C terminus of the LVGC  subunit (Yang et al, 2005(Yang et al, , 2009. Our results in small airways support the hypothesis that LVGC activity is regulated by PKC.…”

Section: Pkc Activation Induces Small Airway Smc Twitchingsupporting

confidence: 78%

Ca²⁺oscillations, Ca²⁺sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Mukherjee¹,

Trice²,

Shinde³

et al. 2013

J Cell Biol

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Section: Pkc Activation Induces Small Airway Smc Twitchingsupporting

confidence: 78%

Ca²⁺oscillations, Ca²⁺sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Mukherjee¹,

Trice²,

Shinde³

et al. 2013

J Cell Biol

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“…It has been demonstrated that L-type Ca 2ϩ channels can be regulated by several types of kinases in different tissues (7,12,28,36). Previous studies confirmed that PKA and PKC phosphorylate serine and threonine residues on the ␣-and ␤-subunits of the L-type Ca 2ϩ channel (34,36,53). Therefore, to evaluate the contribution of PKA to depolarization-induced Ca 2ϩ entry in GH3 cells, we tested the effect of N-[2-(pbromocinnamylamino)ethyl]-5-isoquinoline sulfonamide hydrochloride (H89), a selective PKA inhibitor, on Ca 2ϩ mobilization evoked by 12.5 mM KCl.…”

Section: Methodsmentioning

confidence: 81%

Different kinases regulate activation of voltage-dependent calcium channels by depolarization in GH3 cells

Vela

Pérez-Millán²,

Becú-Villalobos³

et al. 2007

American Journal of Physiology-Cell Physiology

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The L-type Ca2+ channel is the primary voltage-dependent Ca2+-influx pathway in many excitable and secretory cells, and direct phosphorylation by different kinases is one of the mechanisms involved in the regulation of its activity. The aim of this study was to evaluate the participation of Ser/Thr kinases and tyrosine kinases (TKs) in depolarization-induced Ca2+ influx in the endocrine somatomammotrope cell line GH3. Intracellular Ca2+ concentration ([Ca2+]i) was measured using a spectrofluorometric method with fura 2-AM, and 12.5 mM KCl (K+) was used as a depolarization stimulus. K+ induced an abrupt spike (peak) in [Ca2+]i that was abolished in the presence of nifedipine, showing that K+ enhances [Ca2+]i, preferably activating L-type Ca2+ channels. H89, a selective PKA inhibitor, significantly reduced depolarization-induced Ca2+ mobilization in a concentration-related manner when it was applied before or after K+, and okadaic acid, an inhibitor of Ser/Thr phosphatases, which has been shown to regulate PKA-stimulated L-type Ca2+ channels, increased K+-induced Ca2+ entry. When PKC was activated by PMA, the K+-evoked peak in [Ca2+]i, as well as the plateau phase, was significantly reduced, and chelerythrine (a PKC inhibitor) potentiated the K+-induced increase in [Ca2+]i, indicating an inhibitory role of PKC in voltage-dependent Ca2+ channel (VDCC) activity. Genistein, a TK inhibitor, reduced the K+-evoked increase in [Ca2+]i, but, unexpectedly, the tyrosine phosphatase inhibitor orthovanadate reduced not only basal Ca2+ levels but, also, Ca2+ influx during the plateau phase. Both results suggest that different TKs may act differentially on VDCC activation. Activation of receptor TKs with epidermal growth factor (EGF) or vascular endothelial growth factor potentiated K+-induced Ca2+ influx, and AG-1478 (an EGF receptor inhibitor) decreased it. However, inhibition of the non-receptor TK pp60 c-Src enhanced K+-induced Ca2+ influx. The present study strongly demonstrates that a complex equilibrium among different kinases and phosphatases regulates VDCC activity in the pituitary cell line GH3: PKA and receptor TKs, such as vascular endothelial growth factor receptor and EGF receptor, enhance depolarization-induced Ca2+ influx, whereas PKC and c-Src have an inhibitory effect. These kinases modulate membrane depolarization and may therefore participate in the regulation of a plethora of intracellular processes, such as hormone secretion, gene expression, protein synthesis, and cell proliferation, in pituitary cells.

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“…Despite decades of research on the regulation of voltage-gated ion channels by protein phosphorylation, few phosphorylation events that alter ion channel activity have been shown to be physiologically modulated in vivo (43)(44)(45). This is especially true of the positive feedback regulation of L-type and T-type channels by CaMKII.…”

Section: Discussionmentioning

confidence: 99%

Molecular basis for the modulation of native T-type Ca2+ channels in vivo by Ca2+/calmodulin-dependent protein kinase II

Yao¹

2006

Journal of Clinical Investigation

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Ser1928 Is a Common Site for Cav1.2 Phosphorylation by Protein Kinase C Isoforms

Cited by 104 publications

References 61 publications

Ca²⁺oscillations, Ca²⁺sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Ca²⁺oscillations, Ca²⁺sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Different kinases regulate activation of voltage-dependent calcium channels by depolarization in GH3 cells

Molecular basis for the modulation of native T-type Ca2+ channels in vivo by Ca2+/calmodulin-dependent protein kinase II

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Ser1928 Is a Common Site for Cav1.2 Phosphorylation by Protein Kinase C Isoforms

Cited by 104 publications

References 61 publications

Ca2+oscillations, Ca2+sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Ca2+oscillations, Ca2+sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Different kinases regulate activation of voltage-dependent calcium channels by depolarization in GH3 cells

Molecular basis for the modulation of native T-type Ca2+ channels in vivo by Ca2+/calmodulin-dependent protein kinase II

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Ca²⁺oscillations, Ca²⁺sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Ca²⁺oscillations, Ca²⁺sensitization, and contraction activated by protein kinase C in small airway smooth muscle