Calcium/Calmodulin-dependent Protein Kinase II Binds to Raf-1 and Modulates Integrin-stimulated ERK Activation

Illario, Maddalena; Cavallo, Anna Lina; Bayer, Karl; Matola, Tiziana Di; Fenzi, Gianfranco; Rossi, Guido; Vitale, Mario

doi:10.1074/jbc.m305355200

Cited by 143 publications

(129 citation statements)

References 44 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…It has been reported that integrin activation can modify intracellular calcium levels (Coppolino et al, 1997), which in turn, can affect adenylyl cyclase and hence cAMP production. However, in our experiments both the blocking antibody and soluble RGD peptide have no effect in calcium levels as reported previously (Illario et al, 2003). Furthermore, neither the antibody nor peptide alone had an effect on basal or PGE2-stimulated cAMP levels in our assay.…”

Section: Discussionmentioning

confidence: 37%

Integrins regulate opioid receptor signaling in trigeminal ganglion neurons

Berg

Zardeneta²,

Hargreaves

et al. 2007

Neuroscience

View full text Add to dashboard Cite

The binding of integrins to the extracellular matrix results in focal organization of the cytoskeleton and the genesis of intracellular signals that regulate vital neuronal functions. Recent evidence suggests that integrins modulate G-protein coupled receptor (GPCR) signaling in hippocampal neurons. In this study we evaluated the hypothesis that integrins regulate the mu opioid receptor in rat trigeminal ganglion neurons. For these studies, primary cultures of adult rat trigeminal ganglion neurons were used to demonstrate the colocalization of β1 and β3 integrins with mu opioid receptor in caveolin-1-rich membrane fractions, and at focal adhesions sites generated by integrin ligand binding. Furthermore, we show that the mu opioid receptor agonist, DAMGO ([DAla 2 ,N-MePhe 4 ,Gly-ol 5 ]enkephalin), inhibits cAMP accumulation in response to PGE 2 stimulation in bradykinin-primed, but not unprimed, cultured trigeminal ganglia neurons. Application of soluble GRGDS (Gly-Arg-Gly-Asp-Ser) peptides that bind specific integrins (i.e., RGD-binding integrins) completely abolished the DAMGO effect in bradykinin-primed trigeminal ganglia neurons, but did not alter bradykinin-mediated hydrolysis of phosphytidylinositol. Likewise, monospecific anti-β1 and anti-β3 integrin subunit antibodies blocked this DAMGO effect in bradykinin -primed trigeminal ganglia neurons. Indeed, application of anti-β1 integrin subunit actually reversed DAMGO signaling, resulting in increased cAMP accumulation in these cells. This suggests that the relative amounts of specific activated integrins at focal adhesions may govern signaling by the mu opioid receptor, perhaps by altering interactions with G proteins (e.g., Gαi vs. Gαs). Collectively, these data provide the first evidence that specific integrins regulate opioid receptor signaling in sensory neurons. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Cells interact with the extracellular matrix via heterodimeric (αβ) transmembrane receptors, termed integrins (Giancotti and Rouslahti, 1999). Integrins are expressed by virtually every cell type and are known to be involved in the regulation of several vital cell functions, including adhesion, migration, proliferation, and differentiation (Milam et al., 1991, Hynes, 1992, Curley et al., 1999, Giancotti and Rouslahti, 1999, Schlaepfer et al., 1999, Coppolino and Dedhar, 2000, Bouvard et al., 2001, Zamir and Geiger, 2001, Alenghat and Ingber, 2002, Martin et al., 2002, Miranti and Brugge, 2002. Eighteen α and eight β subunits have been identified forming at least 24 different αβ integrins (van der Fli...

show abstract

Section: Discussionmentioning

confidence: 37%

Integrins regulate opioid receptor signaling in trigeminal ganglion neurons

Berg

Zardeneta²,

Hargreaves

et al. 2007

Neuroscience

View full text Add to dashboard Cite

show abstract

“…In other cell types, endogenous Raf-1, but not B-Raf, formed a complex with activated CaMKII that was precipitated by antiCaMKII antibodies and recognized by anti-Raf-1 antibodies. 12,13 The selective CaMKII/Raf isoforms interaction was confirmed in COS-7 (Fig. 2).…”

Section: Introductionmentioning

confidence: 73%

“…Co-immunoprecipitation experiments showed that activated CaMKII interacts with Raf-1 in vivo, and that the complex CaMKII/Raf-1 is necessary for ERK activation from different stimuli. [12][13][14]16 This role of CaMKII in the ERK pathway appears to be a widespread mechanism, as it occurs upon different stimuli (fibronectin-stimulated integrins, serum, insulin, RET/PTC oncogene, Ras V12 ), in a number of different cell types (thyroid cells, fibroblasts, L6 myotubes, Hep3B, NIH-3T3 and COS-7 cells) with few exceptions (colon adenocarcinoma cells LoVo and prostate cancer cells DU-145, data not shown). Nevertheless, the physiological role of the CaMKII/ Raf-1 interplay is likely cell context-dependent, as it participates in and is modulated by the complex crosstalk of signal transduction pathways existing in any living cell.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15][16] CaMKII is an ubiquitous serine/ threonine kinase whose activation is modulated by intracellular whether Ras stimulates CaMKII phosphorylation at Thr286, NIH-3T3 cells were transiently transfected with expression vectors encoding HRas V12 and KRas V12 isoforms. 48 h post-transfection, serum-starved cells were treated for 30 min with the calmodulin inhibitors W7 or TFP, and CaMKII phosphorylation at Thr286 was visualized by western blot using a phosphospecific antibody (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates Raf-1 at serine 338 and mediates Ras-stimulated Raf-1 activation

et al. 2012

Self Cite

View full text Add to dashboard Cite

The calcium/calmodulin-dependent kinase II (CaMKII) participates with Ras to Raf-1 activation, and it is necessary for activation of the extracellular signal-regulated kinase (ERK) by different factors in epithelial and mesenchimal cells. Raf-1 activation is a complex multistep process, and its maximal activation is achieved by phosphorylation at Y341 by Src and at S338 by other kinase/s. Although early data proposed the involvement of p21-activated kinase 3 (Pak3), the kinase phosphorylating S338 remains to be definitively identified. In this study, we verified the hypothesis that CaMKII phosphorylates Raf-1 at Ser338. To do so, we determined the role of CaMKII in Raf-1 and ERK activation by oncogenic Ras and other factors. Serum, fibronectin, Src(Y527) and Ras(V12) activated CaMKII and ERK, at different extents. The inhibition of CaMKII attenuated Raf-1 and ERK activation by all these factors. CaMKII was also necessary for the phosphorylation of Raf-1 at S338 by serum, fibronectin and Ras. Conversely, inhibition of Pak3 activation by blocking phosphatidylinositol-3-kinase was ineffective. The direct phosphorylation of S338 Raf-1 by CaMKII was demonstrated in vitro by interaction of purified kinases. These results demonstrate that Ras activates CaMKII, which, in turn, phosphorylates Raf-1 at S338 and participates in ERK activation upon different stimuli

show abstract

“…[32][33][34] Also, SET overexpression in NIH3T3 cells activates the MAPK/ERK pathway by inhibiting PP2A. 17 In addition, both MAPK/ERK and p38/MAPK activation are involved in the maturation of human monocyte-derived DC.…”

Section: Ectopic Set Stimulates the Expression Of Calciumresponsive Gmentioning

confidence: 99%

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

Kandilci

Grosveld

2005

Leukemia

View full text Add to dashboard Cite

Human SET, a target of chromosomal translocation in human leukemia encodes a highly conserved, ubiquitously expressed, nuclear phosphoprotein. SET mediates many functions including chromatin remodeling, transcription, apoptosis and cell cycle control. We report that overexpression of SET directs differentiation of the human promonocytic cell line U937 along the dendritic cell (DC) pathway, as cells display typical morphologic changes associated with DC fate and express the DC surface markers CD11b and CD86. Differentiation occurs via a calcium-dependent mechanism involving the CaMKII and MAPK/ERK pathways. Similar responses are elicited by interferon-c (IFN-c) treatment with the distinction that IFN-c signaling activates the DNA-binding activity of STAT1 whereas SET overexpression does not. In addition, unlike IFN-c signaling, SET generated stress-induced p38/MAPK activity. Interestingly, IFN-c treatment transiently upregulated endogenous SET in a dose-dependent manner. These results suggest that SET is part of both IFN-c-mediated and stress-mediated cellular responses and that SET induces cell differentiation via calcium and MAPK/ ERK pathways.

show abstract

Calcium/Calmodulin-dependent Protein Kinase II Binds to Raf-1 and Modulates Integrin-stimulated ERK Activation

Cited by 143 publications

References 44 publications

Integrins regulate opioid receptor signaling in trigeminal ganglion neurons

Integrins regulate opioid receptor signaling in trigeminal ganglion neurons

Calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates Raf-1 at serine 338 and mediates Ras-stimulated Raf-1 activation

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

Contact Info

Product

Resources

About