Eicosanoid Activation of Protein Kinase C ϵ

Mikule, Keith; Sunpaweravong, Somkiat; Gatlin, Jesse C.; Pfenninger, Karl H.

doi:10.1074/jbc.m211828200

Cited by 28 publications

(21 citation statements)

References 76 publications

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“…Nevertheless, the two proteins clearly colocalized in growth cones. Similar results were obtained when NB cells were cotransfected with the expression vectors encoding for To confirm the presence of Neurabin I and Rac3 at the tip of extending neurites, neuronal growth cones were isolated from embryonic rat brains by subcellular fractionation (see Materials and Methods; Mikule et al, 2003). The Triton X-100 -soluble fraction (S) of growth cones, enriched in cytosolic and membrane-bound proteins, was separated from the insoluble pellet (P), enriched in cytoskeletal proteins (Haataja et al, 2002).…”

Section: Neurabin I and Rac3 Colocalize At The Growth Cone Of Extendimentioning

confidence: 57%

Rac3-induced Neuritogenesis Requires Binding to Neurabin I

Orioli

Colaluca

Stefanini

et al. 2006

MBoC

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Rac3, a neuronal GTP-binding protein of the Rho family, induces neuritogenesis in primary neurons. Using yeast two-hybrid analysis, we show that Neurabin I, the neuronal F-actin binding protein, is a direct Rac3-interacting molecule. Biochemical and light microscopy studies indicate that Neurabin I copartitions and colocalizes with Rac3 at the growth cones of neurites, inducing Neurabin I association to the cytoskeleton. Moreover, Neurabin I antisense oligonucleotides abolish Rac3-induced neuritogenesis, which in turn is rescued by exogenous Neurabin I but not by Neurabin I mutant lacking the Rac3-binding domain. These results show that Neurabin I mediates Rac3-induced neuritogenesis, possibly by anchoring Rac3 to growth cone F-actin.

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Section: Neurabin I and Rac3 Colocalize At The Growth Cone Of Extendimentioning

confidence: 57%

Rac3-induced Neuritogenesis Requires Binding to Neurabin I

Orioli

Colaluca

Stefanini

et al. 2006

MBoC

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“…These results directly link PKCε mediated signal transduction to ERKs, which are important for neural protection, stress sensing, cell growth, and differentiation. PKCε activity has also been shown to be critical for the process of neural growth cone collapse [86], as well as neurite outgrowth [13].…”

Section: Pkcγ and Pkcε In Neural Tissuesmentioning

confidence: 99%

Protein kinase C as a stress sensor

Barnett

Madgwick

Takemoto

2007

Cellular Signalling

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While there are many reviews which examine the group of proteins known as protein kinase C (PKC), the focus of this article is to examine the cellular roles of two PKCs that are important for stress responses in neurological tissues (PKCγ and ε) and in cardiac tissues (PKCε). These two kinases, in particular, seem to have overlapping functions and interact with an identical target, connexin 43 (Cx43), a gap junction protein which is central to proper control of signals in both tissues. While PKCγ and PKCε both help protect neural tissue from ischemia, PKCε is the primary PKC isoform responsible for responding to decreased oxygen, or ischemia, in the heart. Both do this through Cx43.It is clear that both PKCγ and PKCε are necessary for protection from ischemia. However, the importance of these kinases has been inferred from preconditioning experiments which demonstrate that brief periods of hypoxia protect neurological and cardiac tissues from future insults, and that this depends on the activation, translocation, or ability for PKCγ and/or PKCε to interact with distinct cellular targets, especially Cx43.This review summarizes the recent findings which define the roles of PKCγ and PKCε in cardiac and neurological functions and their relationships to ischemia/reperfusion injury. In addition, a biochemical comparison of PKC γ and PKC ε and a proposed argument for why both forms are present in neurological tissue while only PKC ε is present in heart, are discussed. Finally, the biochemistry of PKCs and future directions for the field are discussed, in light of this new information.

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“…Growth cones treated with lipoxygenase inhibitor that are thus unable to generate 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] remain spread out and attached to the substratum even after significant Sema3A-induced loss of F-actin (Mikule et al, 2002). Likewise, induction of growth cone collapse by thrombin, which requires 12(S)-HETE (de la Houssaye et al, 1999) and PKC activity (Mikule et al, 2003), targets growth cone adhesions independently of its effects on the actin cytoskeleton. Biochemical analyses of isolated growth cones and functional studies of dorsal root ganglion (DRG) growth cones demonstrate that the lipoxygenase product 12(S)-HETE directly and selectively activates PKC (Mikule et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, induction of growth cone collapse by thrombin, which requires 12(S)-HETE (de la Houssaye et al, 1999) and PKC activity (Mikule et al, 2003), targets growth cone adhesions independently of its effects on the actin cytoskeleton. Biochemical analyses of isolated growth cones and functional studies of dorsal root ganglion (DRG) growth cones demonstrate that the lipoxygenase product 12(S)-HETE directly and selectively activates PKC (Mikule et al, 2003). Based upon these data, we hypothesized that the repellents Sema3A and thrombin (and possibly Sema4D; Barberis et al, 2004) activate signaling pathways that affect growth cone adhesion sites via eicosanoid-mediated activation of PKC.…”

Section: Introductionmentioning

confidence: 99%

“…Based upon these data, we hypothesized that the repellents Sema3A and thrombin (and possibly Sema4D; Barberis et al, 2004) activate signaling pathways that affect growth cone adhesion sites via eicosanoid-mediated activation of PKC. A likely candidate effector of this activation is myristoylated, alanine-rich C-kinase substrate (MARCKS), the primary PKC substrate in the growth cone (Mikule et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Myristoylated, Alanine-rich C-Kinase Substrate Phosphorylation Regulates Growth Cone Adhesion and Pathfinding

Gatlin

Estrada-Bernal

Sanford

et al. 2006

MBoC

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Repellents evoke growth cone turning by eliciting asymmetric, localized loss of actin cytoskeleton together with changes in substratum attachment. We have demonstrated that semaphorin-3A (Sema3A)-induced growth cone detachment and collapse require eicosanoid-mediated activation of protein kinase C (PKC) and that the major PKC target is the myristoylated, alanine-rich C-kinase substrate (MARCKS). Here, we show that PKC activation is necessary for growth cone turning and that MARCKS, while at the membrane, colocalizes with ␣ 3 -integrin in a peripheral adhesive zone of the growth cone. Phosphorylation of MARCKS causes its translocation from the membrane to the cytosol. Silencing MARCKS expression dramatically reduces growth cone spread, whereas overexpression of wild-type MARCKS inhibits growth cone collapse triggered by PKC activation. Expression of phosphorylation-deficient, mutant MARCKS greatly expands growth cone adhesion, and this is characterized by extensive colocalization of MARCKS and ␣ 3 -integrin, resistance to eicosanoid-triggered detachment and collapse, and reversal of Sema3A-induced repulsion into attraction. We conclude that MARCKS is involved in regulating growth cone adhesion as follows: its nonphosphorylated form stabilizes integrin-mediated adhesions, and its phosphorylation-triggered release from adhesions causes localized growth cone detachment critical for turning and collapse.

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Eicosanoid Activation of Protein Kinase C ϵ

Cited by 28 publications

References 76 publications

Rac3-induced Neuritogenesis Requires Binding to Neurabin I

Rac3-induced Neuritogenesis Requires Binding to Neurabin I

Protein kinase C as a stress sensor

Myristoylated, Alanine-rich C-Kinase Substrate Phosphorylation Regulates Growth Cone Adhesion and Pathfinding

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