NMAAP1 Maintains M1 Phenotype in Macrophages Through Binding to IP3R and Activating Calcium-related Signaling PathwaysNMAAP1 Maintains M1 Phenotype in Macrophages Through Binding to IP3R and Activating Calcium-related Signaling Pathways

(E-pub Abstract Ahead of Print)

Author(s): Qihui Liu, Pei Zhu, Shanshan Liu, Mengyan Tang, Yuanxin Wang, Yuan Tian, Zheng Jin, Dong Li, Dongmei Yan*.

Journal Name: Protein & Peptide Letters

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Abstract:

NMAAP1 plays a role in regulating macrophage differentiation to the M1 type and exerting antitumoral functions. It is not clear what role and mechanism NMAAP1 does play in the reversal of macrophages from M1 to M2. Our study found that knockdown NMAAP1 in RAW264.7 cells induced macrophage polarization to the M2 type and maintains M1 Phenotype even in the presence of IL-4, a stronger inducer of the M2 type. Additionally, Co-immunoprecipitation revealed a protein-protein interaction between NMAAP1 and IP3R and then activates key molecules in the PKC-dependent Raf/MEK/ERK and Ca2+/CaM/CaMKII signaling pathways. Activation of PKC (Thr638/641), ERK1/2 (Thr202/Tyr204) and CaMKII (Thr286) is involved in the regulation of cell differentiation. Therefore, NMAAP1 interacts with IP3R, which in turn activates the PKC-dependent Raf/MEK/ERK and Ca2+/CaM/CaMKII signaling pathways. These results provide a new explanation of the mechanism underlying M1 differentiation.

Keywords: NMAAP1, macrophage, M1, polarization, IP3R, signal pathway

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(E-pub Abstract Ahead of Print)
DOI: 10.2174/0929866526666190503105343
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