Cyclophilin <scp>A</scp> as a downstream effector of <scp>PI3K/Akt</scp> signalling pathway in multiple myeloma cells

Lin, Zuo-Lin; Wu, Hsin-Jou; Lin, Kuo‐Chih; Hsu, Jung-Hsin

doi:10.1002/cbf.3156

Cited by 7 publications

(2 citation statements)

References 36 publications

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“…Since it has been described that AKT can phosphorylate CyPA 39 , we tested whether this event occurred in our experimental setting. Thus, we immunoprecipitated CyPA from cells treated with TZ or TZ/U0126, and probed with two antibodies specific for phospho-AKT substrates (RXXS/T* and RXRXXS/T*) 40 by WB.…”

mentioning

confidence: 99%

Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr701 phosphorylation

Gaviraghi

Rabellino

Andolfo

et al. 2020

Sci Rep

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ERBB2 is a ligand-less tyrosine kinase receptor expressed at very low levels in normal tissues; when overexpressed, it is involved in malignant transformation and tumorigenesis in several carcinomas. In cancer cells, ERBB2 represents the preferred partner of other members of the ERBB receptor family, leading to stronger oncogenic signals, by promoting both ERK and AKT activation. The identification of the specific signaling downstream of ERBB2 has been impaired by the lack of a ligand and of an efficient way to selectively activate the receptor. In this paper, we found that antibodies (Abs) targeting different epitopes on the ERBB2 extracellular domain foster the activation of ERBB2 homodimers, and surprisingly induce a unique cytostatic signaling cascade promoting an ERK-dependent ERBB2 Thr701 phosphorylation, leading to AKT de-phosphorylation, via PP2A Ser/Thr phosphatases. Furthermore, the immunophilin Cyclophilin A plays a crucial role in this pathway, acting as a negative modulator of AKT de-phosphorylation, possibly by competing with Ser/Thr phosphatases for binding to AKT. Altogether, our data show that Ab recognizing ERBB2 extracellular domain function as receptor agonists, promoting ERBB2 homodimer activation, leading to an anti-proliferative signaling. Thus, the ultimate outcome of ERBB2 activity might depend on the dimerization status: pro-oncogenic in the hetero-, and anti-oncogenic in the homo-dimeric form.

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mentioning

confidence: 99%

Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr701 phosphorylation

Gaviraghi

Rabellino

Andolfo

et al. 2020

Sci Rep

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“…This pathway regulates adhesion of the platelets thrombus development (Seizer et al 2015). CypA was found to be highly phosphorylated in response to interleukin-6 treatment, which was consistent with the accumulation of phosphorylated Akt, suggesting that CypA is phosphorylated by Akt, the downstream effector of the PI3K/Akt pathway (Lin et al 2015). CypA is also implicated in retinoic acid-induced neuronal signaling and differentiation (Song et al 2004).…”

Section: Cyclophilins As Signaling Moleculesmentioning

confidence: 66%

Cyclophilin

Roy¹,

Singh²,

Singla‐Pareek³

et al. 2016

Encyclopedia of Signaling Molecules

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Cyclophilin

Roy¹,

Singh²,

Singla‐Pareek³

et al. 2018

Encyclopedia of Signaling Molecules

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Crk SH3 domain binding guanine nucleotide release protein (C3G), Rap guanine nucleotide exchange factor 1 (RAPGEF1), Guanine nucleotide-releasing factor 2 (GRF2) 620 C3G 622 C3G C3G 623 C Downregulated Fernandez et al. 2008 Lymphoproliferative disorder Mutation, Y572C Parker et al. 2016 Human prostate carcinoma Regulates PLCg1-mediated adhesion Peak et al. 2008 Juvenile neuronal ceroid lipofuscinosis Upregulated Lebrun et al. 2011 624 C3G fate determinant. While its catalytic activity enables activation of small GTPases of Ras family, it also has cellular roles independent of its catalytic activity. The fact that other Rap1 GEFs do not compliment C3G during mammalian embryonic development suggests important noncatalytic functions, or its ability to activate other GTPases. Recent studies have shown that altered C3G levels are associated with human cancers and other disorders, suggesting its role in maintaining homeostasis in adult tissues.

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Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells

Cited by 7 publications

References 36 publications

Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr701 phosphorylation

Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr701 phosphorylation

Cyclophilin

Cyclophilin

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