التفاصيل البيبلوغرافية
| العنوان: |
Dynamic interplay between nitration and phosphorylation of tubulin cofactor B in the control of microtubule dynamics. |
| المؤلفون: |
Rayala, Suresh K.1, Martin, Emil2, Sharina, Iraida G.2, Molli, Poonam R.1, Xiaoping Wang3, Jacobson, Raymond3, Murad, Fend2 ferid.murad@uth.tmc.edu, Kumar, Rakesh1,3,4 rkumar@mdanderson.org |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America. 12/4/2007, Vol. 104 Issue 49, p19470-19475. 6p. 5 Graphs. |
| مصطلحات موضوعية: |
*TUBULINS, *EUKARYOTIC cells, *PHOSPHORYLATION, *CYTOSKELETON formation, *NITRIC oxide, *PROTEIN synthesis, *PHYSIOLOGY |
| مستخلص: |
Tubulin cofactor B (TCoB) plays an important role in microtubule dynamics by facilitating the dimerization of α- and β-tubulin. Recent evidence suggests that p21-activated kinase 1 (Pak1), a major signaling nodule in eukaryotic cells. phosphorylates TCoB on Ser-65 and Ser-128 and plays an essential role in microtubule regrowth. However, to date, no upstream signaling molecules have been identified to antagonize the functions of TCoB, which might help in maintaining the equilibrium of microtubules. Here, we discovered that TCoB is efficiently nitrated, mainly on Tyr-64 and Tyr-98, and nitrated-TCoB attenuates the synthesis of new microtubules. In addition, we found that nitration of TCoB antagonizes signaling-dependent phosphorylation of TCoB, whereas optimal nitration of TCoB requires the presence of functional Paki phosphorylation sites, thus providing a feedback mechanism to regulate phosphorylation-dependent MT regrowth. Together these findings identified TCoB as the third cytoskeleton protein to be nitrated and suggest a previously undescribed mechanism, whereby growth factor signaling may coordinately integrate nitric oxide signaling in the regulation of microtubule dynamics. [ABSTRACT FROM AUTHOR] |
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