Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Smooth muscle cell (SMC) phenotypic modulation, primarily driven by PDGFRβ signaling, is implicated in occlusive cardiovascular diseases. However, the promotive and restrictive regulation mechanism of PDGFRβ and the role of protein tyrosine phosphatase non-receptor type 14 (PTPN14) in neointimal hyperplasia remain unclear. Our study observes a marked upregulation of PTPN14 in SMCs during neointimal hyperplasia. PTPN14 overexpression exacerbates neointimal hyperplasia in a phosphatase activity-dependent manner, while SMC-specific deficiency of PTPN14 mitigates this process in mice. RNA-seq indicates that PTPN14 deficiency inhibits PDGFRβ signaling-induced SMC phenotypic modulation. Moreover, PTPN14 interacts with intracellular region of PDGFRβ and mediates its dephosphorylation on Y692 site. Phosphorylation of PDGFRβY692 negatively regulates PDGFRβ signaling activation. The levels of both PTPN14 and phospho-PDGFRβY692 are correlated with the degree of stenosis in human coronary arteries. Our findings suggest that PTPN14 serves as a critical modulator of SMCs, promoting neointimal hyperplasia. PDGFRβY692, dephosphorylated by PTPN14, acts as a self-inhibitory site for controlling PDGFRβ activation. © 2024. The Author(s).

Citation

Qiannan Ma, Xue He, Xue Wang, Guobing Zhao, Yanhong Zhang, Chao Su, Minxin Wei, Kai Zhang, Ming Liu, Yi Zhu, Jinlong He. PTPN14 aggravates neointimal hyperplasia via boosting PDGFRβ signaling in smooth muscle cells. Nature communications. 2024 Aug 27;15(1):7398

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 39191789

View Full Text