Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance

Aifa, Sami; Johansen, Knut; Nilsson, Ulrika K.; Liedberg, Bo; Lundström, Ingemar; Svensson, Samuel

doi:10.1016/s0898-6568(02)00034-7

Cited by 34 publications

(41 citation statements)

References 47 publications

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“…All three a 1 -AR subtypes couple to G q and result in activation of phospholipase C with an increase in inositol triphosphate and subsequent mobilization of intracellular Ca 21 , which leads to activation of the calcium/calmodulin (Ca 21 /CaM) pathway (Wu et al, 1992;Bylund et al, 1994;Della Rocca et al, 1997;Koshimizu et al, 2003). The Ca 21 /CaM pathway directly and indirectly influences EGFR and has a regulatory function in EGFR signaling (Murasawa et al, 1998;Aifa et al, 2002;Li and Villalobo, 2002;Sanchez-Gonzalez et al, 2010). Other important signaling molecules activated by a 1 -AR are the Src (Han et al, 2008) and PI3K, which are also implicated in EGFR transactivation.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Ulu

Henning

Güner

et al. 2013

J Pharmacol Exp Ther

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Transactivation of epidermal growth factor receptor (EGFR) by a 1 -adrenoceptor (a 1 -AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all a 1 -AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster ovary (CHO) cells stably expressing one subtype of a 1 -AR were transiently transfected with EGFR. The transactivation mechanism was examined both by coexpression of a chimeric erythropoietin (EPO)-EGFR with an extracellular EPO and intracellular EGFR domain, and by pharmacologic inhibition of external and internal signaling routes. All three a 1 -AR subtypes transactivated EGFR, which was dependent on the increase in intracellular calcium. The EGFR kinase inhibitor AG1478 [4-(39-chloroanilino)-6,7-dimethoxyquinazoline] abrogated a 1A -AR and a 1D -AR induced phosphorylation of EGFR, but both the inhibition of matrix metalloproteinases by GM6001or blockade of EGFR by cetuximab did not. Stimulation of a 1A -AR and a 1D -AR also induced phosphorylation of EPO-EGFR chimeric receptors. Moreover, a 1A -AR stimulation enhanced phosphorylation of extracellular signal regulated kinase (ERK) 1/2 and serine-threonine kinases (Akt), which were both unaffected by AG1478, indicating that ERK1/2 and Akt phosphorylation is independent of EGFR transactivation. Accordingly, inhibitors of ERK1/2 or Akt did not influence the a 1A -AR-mediated EGFR transactivation. Inhibition of calcium/ calmodulin-dependent kinase II (CaMKII), phosphatidylinositol 3-kinase (PI3K), and Src, however, did block EGFR transactivation by a 1A -AR and a 1D -AR. These findings demonstrate that all a 1 -AR subtypes transactivate EGFR, which is dependent on an intracellular signaling route involving an increase in calcium and activation of CaMKII, PI3K, and Src, but not the of ERK1/2 and Akt pathways.

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Section: Discussionmentioning

confidence: 99%

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Ulu

Henning

Güner

et al. 2013

J Pharmacol Exp Ther

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“…Amino acids in this region have been shown to serve as binding and phosphorylation sites for signaling molecules. [45][46][47][48][49][50] The importance of the JM domain in signaling is evident from several mutations, deletions and insertions in this domain that can lead to cancer. [51][52][53] In addition, recent studies have provided evidence for the active role of the JM domains in regulating RTK activity.…”

Section: Juxtamembrane Domainsmentioning

confidence: 99%

Receptor tyrosine kinase transmembrane domains

Hristova

2010

Cell Adhesion & Migration

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“…Although one must obviously be cautious when interpreting cell biological experiments with CaM inhibitors, we do wish to suggest that they can provide useful information about cellular processes. For example, Ca 2ϩ /CaM binds to the EGFR (18,20) and to peptides corresponding to its JM region (19,21,53). Does this binding contribute to the activation of the receptor?…”

Section: W-7/w-13/w-12 Bind Strongly To Phospholipid Membranes Reducmentioning

confidence: 99%

Membrane-permeable Calmodulin Inhibitors (e.g. W-7/W-13) Bind to Membranes, Changing the Electrostatic Surface Potential

Sengupta

Ruano

Tebar

et al. 2007

Journal of Biological Chemistry

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Membrane-permeable calmodulin inhibitors, such as the napthalenesulfonamide derivatives W-7/W-13, trifluoperazine, and calmidazolium, are used widely to investigate the role of calcium/calmodulin (Ca 2؉ /CaM) in living cells. If two chemically different inhibitors (e.g. W-7 and trifluoperazine) produce similar effects, investigators often assume the effects are due to CaM inhibition. Zeta potential measurements, however, show that these amphipathic weak bases bind to phospholipid vesicles at the same concentrations as they inhibit Ca 2؉ /CaM; this suggests that they also bind to the inner leaflet of the plasma membrane, reducing its negative electrostatic surface potential. This change will cause electrostatically bound clusters of basic residues on peripheral (e.g. Src and K-Ras4B) and integral (e.g. epidermal growth factor receptor (EGFR)) proteins to translocate from the membrane to the cytoplasm. We measured inhibitor-mediated translocation of a simple basic peptide corresponding to the calmodulin-binding juxtamembrane region of the EGFR on model membranes; W-7/W-13 causes translocation of this peptide from membrane to solution, suggesting that caution must be exercised when interpreting the results obtained with these inhibitors in living cells. We present evidence that they exert dual effects on autophosphorylation of EGFR; W-13 inhibits epidermal growth factordependent EGFR autophosphorylation under different experimental conditions, but in the absence of epidermal growth factor, W-13 stimulates autophosphorylation of the receptor in four different cell types. Our interpretation is that the former effect is due to W-13 inhibition of Ca 2؉

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Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance

Cited by 34 publications

References 47 publications

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Receptor tyrosine kinase transmembrane domains

Membrane-permeable Calmodulin Inhibitors (e.g. W-7/W-13) Bind to Membranes, Changing the Electrostatic Surface Potential

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Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance

Cited by 34 publications

References 47 publications

Intracellular Transactivation of Epidermal Growth Factor Receptor byα1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Intracellular Transactivation of Epidermal Growth Factor Receptor byα1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Receptor tyrosine kinase transmembrane domains

Membrane-permeable Calmodulin Inhibitors (e.g. W-7/W-13) Bind to Membranes, Changing the Electrostatic Surface Potential

Contact Info

Product

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About

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells