Integrin-linked Kinase Regulates the Nuclear Entry of the c-Jun Coactivator α-NAC and Its Coactivation Potency

Quélo, Isabelle; Gauthier, Claude; Hannigan, Gregory E.; Dedhar, Shoukat; St‐Arnaud, René

doi:10.1074/jbc.m406310200

Cited by 48 publications

(51 citation statements)

References 56 publications

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“…In addition to acting as a protein translation chaperone, NACA also functions as a transcriptional coactivator in conjunction with an acidic activator (28,29). NACA may be phosphorylated by several kinases in vitro and its function as a transcriptional coactivator is regulated by phosphorylation change (30,31). Findings of the present study have shown that the phosphorylation level of NACA was not altered in the inflammatory pain model compared to the control, but that EA treatment increased the phosphorylation level.…”

supporting

confidence: 55%

Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model

Lee

Kim

et al. 2012

Mol Med Report

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Abstract. The phosphorylation changes of nociceptive signaling proteins in the spinal cord dorsal horn (SCDH) are important in creating exaggerated pain following peripheral inflammation. Electroacupuncture (EA) has been widely used to relieve acute and chronic inflammatory pain in human and experimental pain models. In the present study, we performed a phosphoproteomic analysis to investigate whether EA alters protein phosphorylation in SCDH to attenuate pain development. Inflammatory hyperalgesia was induced by intraplantar injection of complete Freund's adjuvant (CFA) into the rat hind paw. EA treatment at ST36 and SP6 acupoints alleviated thermal hyperalgesia of the CFA-induced inflammatory pain model rats. The SCDH proteins from the control, inflammatory pain model and EA treatment rats were separated by 2-dimensional gel electrophoresis and the alterations in phosphoproteins were detected by Pro-Q Diamond staining. Eight proteins were differentially phosphorylated following EA treatment in the inflammatory pain model. Aldolase C, nascent polypeptide-associated complex α, stress-induced phosphoprotein 1 and heat shock protein 90 were identified as phosphoproteins whose expression was increased, whereas GDP dissociation inhibitor 1, thiamine triphosphatase, phosphoglycerate kinase 1 and 14-3-3 γ were phosphoproteins whose expression was decreased. This is the first phosphoproteomic screening study to elucidate the working mechanisms of EA analgesia. The results suggest that the regulation of cellular pathways in which the identified proteins are involved may be associated with an EA analgesic mechanism. IntroductionPeripheral inflammation frequently leads to the development of chronic pain, which is a leading cause of disability globally. In inflammatory pain, peripheral stimuli activate primary afferent neurons and are transmitted to secondary sensory neurons in the spinal cord dorsal horn (SCDH). Persistent noxious stimuli increase the excitability of secondary neurons in the SCDH and decrease the pain threshold. Early studies attributed this central sensitization to the facilitated synaptic transmission of nociceptive signals in the SCDH (1,2). Various signaling molecules such as glutamate receptors, protein kinase A (PKA), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), Ca 2+ -/calmodulin-dependent kinase II (CaMKII) and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-jun N-terminal kinase (JNK), have been shown to be involved in altered nociceptive processing in the SCDH (3-5). Activation of these molecules is capable of inducing signaling cascades that lead to the subsequent expression of pain-associated genes such as prodynorphin, neurokinin-1 (NK-1) and cyclooxygenase-2 (COX-2) (6,7).Acupuncture, a traditional therapeutic method in oriental medicine, has long been clinically used to relieve pain. In particular, electroacupuncture (EA), where electrical stimulation is applied to acupuncture needles, is widely used in clinical an...

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supporting

confidence: 55%

Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model

Lee

Kim

et al. 2012

Mol Med Report

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“…light chain phosphatase, MYPT1 (Mura´nyi et al, 2002) and a-NAC (Quelo et al, 2004). Following the initial discovery of ILK and in vitro characterization of its kinase activity (Hannigan et al, 1996), a research question related to the mechanism of activation of smooth-muscle contraction provided independent support for the conclusion that ILK is a bona fide protein serine/threonine kinase.…”

Section: Does Ilk Fulfill the Biochemical And Biological Criteria Shomentioning

confidence: 98%

Integrin-linked kinase: Not so ‘pseudo’ after all

McDonald²,

et al. 2011

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“…The phosphorylation of GSK3 by ILK regulates pathways that lead to the activation of activator protein 1 (AP1) and -catenin-LEF transcription factors, which in turn stimulate matrix metalloprotease 9 (MMP9) and cyclin D1, respectively (Hannigan et al, 2005). ILK also phosphorylates NAC, a transcriptional coactivator of AP1 (Quelo et al, 2004). Finally, ILK can modulate cell spreading, migration and cytoskeletal organization by activating PAK-interactive exchange factor ( -PIX, also known as ARHGEF6), a guanine-nucleotide exchange factor (GEF) for Rac1 and Cdc42 (Filipenko et al, 2005), and by activating cofilin through an interaction with phosphorylated Src (Kim et al, 2008).…”

Section: Ilk and Cell Signalingmentioning

confidence: 99%

Integrin-linked kinase – essential roles in physiology and cancer biology

McDonald

Fielding

Dedhar

2008

Journal of Cell Science

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305

322

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Integrin-linked kinase (ILK) is a multifunctional intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The use of recently developed Cre-lox-driven recombination and RNAinterference technologies has enabled the evaluation of the physiological roles of ILK in several major organ systems. Significant developmental and tissue-homeostasis defects occur when the gene that encodes ILK is deleted, whereas the expression of ILK is often elevated in human malignancies. Although the cause(s) of ILK overexpression remain to be fully elucidated, accumulating evidence suggests that its oncogenic capacity derives from its regulation of several downstream targets that provide cells with signals that promote proliferation, survival and migration, supporting the concept that ILK is a relevant therapeutic target in human cancer. Furthermore, a global analysis of the ILK 'interactome' has yielded several novel interactions, and has revealed exciting and unexpected cellular functions of ILK that might have important implications for the development of effective therapeutic agents.

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Integrin-linked Kinase Regulates the Nuclear Entry of the c-Jun Coactivator α-NAC and Its Coactivation Potency

Cited by 48 publications

References 56 publications

Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model

Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model

Integrin-linked kinase: Not so ‘pseudo’ after all

Integrin-linked kinase – essential roles in physiology and cancer biology

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