Unknown

Dataset Information

0

Beta-Actin regulates platelet nitric oxide synthase 3 activity through interaction with heat shock protein 90.


ABSTRACT: Cytoskeletal proteins are crucial in maintaining cellular structure and, in certain cell types, also play an essential role in motility and shape change. Nitric oxide (NO) is an important paracrine mediator of vascular and platelet function and is produced in the vasculature by the enzyme NO synthase type 3 (NOS-3). Here, we demonstrate in human platelets that the polymerization state of beta-actin crucially regulates the activation state of NOS-3, and hence NO formation, through altering its binding of heat shock protein 90 (Hsp90). We found that NOS-3 binds to the globular, but not the filamentous, form of beta-actin, and the affinity of NOS-3 for globular beta-actin is, in turn, increased by Hsp90. Formation of this ternary complex among NOS-3, globular beta-actin, and Hsp90, in turn, results in an increase in both NOS activity and cyclic guanosine-3',5'-monophosphate, an index of bioactive NO, as well as an increased rate of Hsp90 degradation, thus limiting the duration for which NOS-3 remains activated. These observations suggest that beta-actin plays a critical role in regulating NO formation and signaling in platelets.

SUBMITTER: Ji Y 

PROVIDER: S-EPMC1885589 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

beta-Actin regulates platelet nitric oxide synthase 3 activity through interaction with heat shock protein 90.

Ji Yong Y   Ferracci Géraldine G   Warley Alice A   Ward Malcolm M   Leung Kit-Yi KY   Samsuddin Salma S   Lévêque Christian C   Queen Lindsay L   Reebye Vikash V   Pal Pallavi P   Gkaliagkousi Eugenia E   Seager Michael M   Ferro Albert A  

Proceedings of the National Academy of Sciences of the United States of America 20070514 21


Cytoskeletal proteins are crucial in maintaining cellular structure and, in certain cell types, also play an essential role in motility and shape change. Nitric oxide (NO) is an important paracrine mediator of vascular and platelet function and is produced in the vasculature by the enzyme NO synthase type 3 (NOS-3). Here, we demonstrate in human platelets that the polymerization state of beta-actin crucially regulates the activation state of NOS-3, and hence NO formation, through altering its bi  ...[more]

Similar Datasets

| S-EPMC1221746 | biostudies-other
| S-EPMC7722166 | biostudies-literature
| S-EPMC2836036 | biostudies-literature
| S-EPMC1382336 | biostudies-literature
2021-01-18 | GSE164521 | GEO
| S-EPMC3359791 | biostudies-literature
| S-EPMC2725775 | biostudies-literature
2023-06-01 | PXD040726 | Pride
| S-EPMC1218042 | biostudies-other
| S-EPMC7719093 | biostudies-literature