| Autor: |
Kun Lu, Katherine, Armstrong, Shayn E., Ginnan, Roman, Singer, Harold A. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Cell Physiology; Nov2005, Vol. 289 Issue 5, pC1343-C1350, 8p, 3 Diagrams, 6 Graphs |
| Abstrakt: |
Cell adhesion-dependent activation of ERK½ has been linked functionally to focal adhesion dynamics. We previously reported that in adherent vascular smooth muscle (VSM) cells, CaMKII mediates ERK½ activation in response to Ca2+-mobilizing stimuli. In the present study, we tested whether CaMKII regulates ERK½ signaling in response to VSM cell adhesion. Using an antibody that specifically recognizes CaMKII auto-phosphorylated on Thr287, we determined that CaMKII is rapidly activated (within 1 mm) after the adherence of cells on multiple ECM substrates. Activation of CaMKII on fibronectin was unaffected in cells overexpressing focal adhesion kinase (FAK)-related nonkinase (FRNK), an endogenous inhibitor of FAK. Furthermore, CaMKII was rapidly and robustly activated in VSM cells plated on poly-L-lysine. These results suggest that adhesion-dependent CaMKII activation is integrin independent. Adhesion-dependent FAK activation on fibronectin was not affected in cells treated with the selective CaMKII inhibitor KN-93 (30 µM) or in cells in which the expression of CaMKII with small interfering RNA (siRNA) was suppressed, although. tyrosine phosphorylation of paxillin was inhibited in CaMKII-δ2-suppressed cells. Sustained ERK½ activation that was dependent on FAK activation (inhibited by FRNK) was also attenuated by CaMKII inhibition or siRNA-mediated gene silencing. Rapid ERK½ activation that preceded FAK and paxillin activation was detected upon VSM cell adhesion to poly-L-lysine, and this response was inhibited by CaMKII gene silencing. These results indicate that integrin-independent CaMKII activation is an early signal during VSM cell adhesion that positively modulates ERK½ signaling through FAK-dependent and FAK-independent mechanisms. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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