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• W4313333679 endingPage "1401" @default.
• W4313333679 startingPage "1393" @default.
• W4313333679 abstract "Abstract Phosphoinositides that are phosphorylated at the D3 position have been reported to activate an atypical, Ca2-independent protein kinase C (PKC) isoform designated PKC-ζ, and overexpression of this enzyme leads to monocytic differentiation. In this study, we cultured human HL-60 promyeloid cells with vitamin D3 and insulin-like growth factor-I (IGF-I), a 70-amino-acid peptide that activates phosphatidylinositol 3′-kinase (PI 3-kinase) in murine promyeloid cells. Two days later, the proportion of cells differentiating into macrophages in serum-free medium, as assessed by expression of the α-subunit of the β2 integrin CD11b, increased from 5 ± 1% to 25 ± 3%. Addition of IGF-I increased the proportion of cells differentiating into CD11b-positive macrophages to 78 ± 5%. In the absence of vitamin D3, IGF-I did not induce expression of CD11b (6 ± 1%). The IGF-I-promoted macrophage differentiation was blocked specifically by preincubation of HL-60 cells with a mAb (αIR3) directed against the IGF type I receptor. Similarly, pretreatment of cells with either αIR3 or an IGF-binding protein, IGFBP-3, led to a 75% inhibition of CD11b expression when cells were cultured with vitamin D3 in serum-containing medium. IGF-I, but not vitamin D3, caused a sevenfold increase in the enzymatic activity of both PI 3-kinase and atypical PKC-ζ. Inhibition of IGF-I-inducible PI 3-kinase with either wortmannin or LY294002 abrogated the IGF-I-induced activation of PKC-ζ and totally blocked the enhancement in macrophage differentiation caused by IGF-I. These data establish that PKC-ζ is a putative downstream target of PI 3-kinase that is activated during IGF-I-promoted macrophage differentiation." @default.
• W4313333679 created "2023-01-06" @default.
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• W4313333679 date "1998-02-01" @default.
• W4313333679 modified "2023-10-09" @default.
• W4313333679 title "Activation of Protein Kinase C-ζ and Phosphatidylinositol 3′-Kinase and Promotion of Macrophage Differentiation by Insulin-Like Growth Factor-I" @default.
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• W4313333679 doi "https://doi.org/10.4049/jimmunol.160.3.1393" @default.
• W4313333679 hasPublicationYear "1998" @default.
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