scholarly journals Sorbitol activates atypical protein kinase C and GLUT4 glucose transporter translocation/glucose transport through proline-rich tyrosine kinase-2, the extracellular signal-regulated kinase pathway and phospholipase D

2002 ◽  
Vol 362 (3) ◽  
pp. 665 ◽  
Author(s):  
Mini P. SAJAN ◽  
Gautam BANDYOPADHYAY ◽  
Yoshinori KANOH ◽  
Mary L. STANDAERT ◽  
Michael J. QUON ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Phospholipase D ◽  
Glucose Transporter ◽  
Extracellular Signal Regulated Kinase ◽  
Kinase C ◽  
Tyrosine Kinase 2 ◽  
Extracellular Signal ◽  
Kinase Pathway

scholarly journals Glucose Activates Protein Kinase C-ζ/λ through Proline-rich Tyrosine Kinase-2, Extracellular Signal-regulated Kinase, and Phospholipase D

2001 ◽  
Vol 276 (38) ◽  
pp. 35537-35545 ◽  
Author(s):  
Gautam Bandyopadhyay ◽  
Mini P. Sajan ◽  
Yoshinori Kanoh ◽  
Mary L. Standaert ◽  
Michael J. Quon ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Phospholipase D ◽  
Extracellular Signal Regulated Kinase ◽  
Kinase C ◽  
Tyrosine Kinase 2 ◽  
Extracellular Signal

Sorbitol activates atypical protein kinase C and GLUT4 glucose transporter translocation/glucose transport through proline-rich tyrosine kinase-2, the extracellular signal-regulated kinase pathway and phospholipase D

2002 ◽  
Vol 362 (3) ◽  
pp. 665-674 ◽  
Author(s):  
Mini P. SAJAN ◽  
Gautam BANDYOPADHYAY ◽  
Yoshinori KANOH ◽  
Mary L. STANDAERT ◽  
Michael J. QUON ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Transport ◽  
Phospholipase D ◽  
Glucose Transporter ◽  
Erk Pathway ◽  
Glut4 Translocation ◽  
Extracellular Signal Regulated Kinase ◽  
Kinase C ◽  
Tyrosine Kinase 2 ◽  
Extracellular Signal

Sorbitol, ‘osmotic stress’, stimulates GLUT4 glucose transporter translocation to the plasma membrane and glucose transport by a phosphatidylinositol (PI) 3-kinase-independent mechanism that reportedly involves non-receptor proline-rich tyrosine kinase-2 (PYK2) but subsequent events are obscure. In the present study, we found that extracellular signal-regulated kinase (ERK) pathway components, growth-factor-receptor-bound-2 protein, son of sevenless (SOS), RAS, RAF and mitogen-activated protein (MAP) kinase/ERK kinase, MEK(−1), operating downstream of PYK2, were required for sorbitol-stimulated GLUT4 translocation/glucose transport in rat adipocytes, L6 myotubes and 3T3/L1 adipocytes. Furthermore, sorbitol activated atypical protein kinase C (aPKC) through a similar mechanism depending on the PYK2/ERK pathway, independent of PI 3-kinase and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1). Like PYK2/ERK pathway components, aPKCs were required for sorbitol-stimulated GLUT4 translocation/glucose transport. Interestingly, sorbitol stimulated increases in phospholipase D (PLD) activity and generation of phosphatidic acid (PA), which directly activated aPKCs. As with aPKCs and glucose transport, sorbitol-stimulated PLD activity was dependent on the ERK pathway. Moreover, PLD-generated PA was required for sorbitol-induced activation of aPKCs and GLUT4 translocation/glucose transport. Our findings suggest that sorbitol sequentially activates PYK2, the ERK pathway and PLD, thereby increasing PA, which activates aPKCs and GLUT4 translocation. This mechanism contrasts with that of insulin, which primarily uses PI 3-kinase, D3-PO4 polyphosphoinositides and PDK-1 to activate aPKCs.

scholarly journals Adenylate cyclase, cyclic AMP and extracellular-signal-regulated kinase-2 in airway smooth muscle: modulation by protein kinase C and growth serum

1995 ◽  
Vol 306 (3) ◽  
pp. 723-726 ◽  
Author(s):  
N Moughal ◽  
P A Stevens ◽  
D Kong ◽  
S Pyne ◽  
N J Pyne
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Airway Smooth Muscle ◽  
Phospholipase D ◽  
Extracellular Signal Regulated Kinase ◽  
Kinase C ◽  
Extracellular Signal

Bradykinin and phorbol 12-myristate 13-acetate stimulate adenylate cyclase activity in serum-depleted cultured airway smooth muscle via a protein kinase C (PKC)-dependent pathway. The probable target is the type II adenylate cyclase, which can integrate coincident signals from both PKC and Gs. Therefore, activation of Gs (by cholera-toxin pre-treatment) amplified the bradykinin-stimulated cyclic AMP signal and concurrently attenuated the partial activation of extracellular-signal-regulated kinase-2 (ERK-2) by bradykinin. We have previously demonstrated that, in order to induce full activation of ERK-2 with bradykinin, it is necessary to obliterate PKC-stimulated cyclic AMP formation. We concluded that the cyclic AMP signal limits the magnitude of ERK-2 activation [Pyne, Moughal, Stevens, Tolan and Pyne (1994) Biochem. J. 304, 611-616]. The present study indicates that the bradykinin-stimulated ERK-2 pathway is entirely cyclic AMP-sensitive, and suggests that coincident signal detection by adenylate cyclase may be an important physiological route for the modulation of early mitogenic signalling. Furthermore, the direct inhibition of adenylate cyclase activity enables bradykinin to induce DNA synthesis, indicating that the PKC-dependent activation of adenylate cyclase limits entry of cells into the cell cycle. These studies suggest that the mitogenicity of an agonist may be governed, in part, by its ability to stimulate an inhibitory cyclic AMP signal pathway in the cell. The activation of adenylate cyclase by PKC appears to be downstream of phospholipase D. However, in cells that were maintained in growth serum (i.e. were not growth-arrested), bradykinin was unable to elicit a PKC-stimulated cyclic AMP response. The lesion in the signal-response coupling was not at the level of either the receptor or phospholipase D, which remain functionally operative and suggests modification occurs at either PKC or adenylate cyclase itself. These studies are discussed with respect to the cell signal regulation of mitogenesis in airway smooth muscle.

scholarly journals Tamoxifen suppresses paclitaxel-, vincristine-, and bortezomib-induced neuropathy via inhibition of the protein kinase C/extracellular signal-regulated kinase pathway

Tumor Biology ◽  
2018 ◽  
Vol 40 (10) ◽  
pp. 101042831880867 ◽  
Author(s):  
Masanobu Tsubaki ◽  
Tomoya Takeda ◽  
Mikihiro Matsumoto ◽  
Natsuki Kato ◽  
Shota Yasuhara ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Dorsal Root ◽  
Extracellular Signal Regulated Kinase ◽  
Chemotherapy Drugs ◽  
Kinase C ◽  
Extracellular Signal ◽  
Chemotherapy Agents ◽  
Kinase Pathway

Chemotherapy-induced neuropathy is a highly problematic, dose-limiting effect of potentially curative regimens of cancer chemotherapy. When neuropathic pain is severe, patients often either switch to less-effective chemotherapy agents or choose to discontinue chemotherapy entirely. Conventional chemotherapy drugs used to treat lung and breast cancer, multiple myeloma, and lymphoma include paclitaxel, vincristine, and bortezomib. Approximately 68% of patients receiving these anticancer drugs develop neuropathy within the first month of treatment, and while strategies to prevent chemotherapy-induced neuropathy have been investigated, none have yet been proven as effective. Recent reports suggest that chemotherapy-induced neuropathy is associated with signal transduction molecules, including protein kinase C and mitogen-activated protein kinases. It is currently unclear whether protein kinase C inhibition can prevent chemotherapy-induced neuropathy. In this study, we found that tamoxifen, a protein kinase C inhibitor, suppressed paclitaxel-, vincristine-, and bortezomib-induced cold and mechanical allodynia in mice. In addition, chemotherapy drugs induce neuropathy via the protein kinase C/extracellular signal-regulated kinase pathway in the spinal cord in lumbar segments 4–6 and dorsal root ganglions. In addition, tamoxifen was shown to act synergistically with paclitaxel to inhibit tumor-growth in mice injected with tumor cells. Our results indicated that paclitaxel-, vincristine-, and bortezomib-induced neuropathies were associated with the protein kinase C/extracellular signal-regulated kinase pathway in the lumbar spinal cord and dorsal root ganglions, which suggest that protein kinase C inhibitors may be therapeutically effective for the prevention of chemotherapy-induced neuropathy when administered with standard chemotherapy agents.

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