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Supplementary Figure 1 from Activated Ca2+/Calmodulin-Dependent Protein Kinase IIγ Is a Critical Regulator of Myeloid Leukemia Cell Proliferation

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posted on 2023-03-30, 18:04 authored by Jutong Si, Steven J. Collins
Supplementary Figure 1 from Activated Ca2+/Calmodulin-Dependent Protein Kinase IIγ Is a Critical Regulator of Myeloid Leukemia Cell Proliferation

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ARTICLE ABSTRACT

Ca2+ signaling is an important component of signal transduction pathways regulating B and T lymphocyte proliferation, but the functional role of Ca2+ signaling in regulating myeloid leukemia cell proliferation has been largely unexplored. We observe that the activated (autophosphorylated) Ca2+/calmodulin-dependent protein kinase IIγ (CaMKIIγ) is invariably present in myeloid leukemia cell lines as well as in the majority of primary acute myelogenous leukemia patient samples. In contrast, myeloid leukemia cells induced to terminally differentiate or undergo growth arrest display a marked reduction in this CaMKIIγ autophosphorylation. In cells harboring the bcr-abl oncogene, the activation (autophosphorylation) of CaMKIIγ is regulated by this oncogene. Moreover, inhibition of CaMKIIγ activity with pharmacologic agents, dominant-negative constructs, or short hairpin RNAs inhibits the proliferation of myeloid leukemia cells, and this is associated with the inactivation/down-regulation of multiple critical signal transduction networks involving the mitogen-activated protein kinase, Janus-activated kinase/signal transducers and activators of transcription (Jak/Stat), and glycogen synthase kinase (GSK3β)/β-catenin pathways. In myeloid leukemia cells, CaMKIIγ directly phosphorylates Stat3 and enhances its transcriptional activity. Thus, CaMKIIγ is a critical regulator of multiple signaling networks regulating the proliferation of myeloid leukemia cells. Inhibiting CaMKIIγ may represent a novel approach in the targeted therapy of myeloid leukemia. [Cancer Res 2008;68(10):3733–42]

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