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Published on: March 12, 2015
Interferon gamma induces the myristoylation of a 48-kDa protein in macrophages
A A Aderem1, D E Marratta, Z A Cohn
1Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Abstract:
The lymphokine interferon gamma (IFN-gamma) induces the selective myristoylation of a macrophage protein with an apparent molecular mass of 48 kDa. The myristic acid-protein bond is resistant to treatment with hydroxylamine, suggesting that the fatty acid moiety is in an amide linkage. As little as 1 unit of IFN-gamma per ml induces the myristoylation of the 48-kDa protein, with half-maximal myristoylation being observed with 4 units/ml. The effect is observed within 1 hr after exposure to IFN-gamma and is maximal by 3-4 hr, after which it declines. IFN-alpha does not induce the myristoylation of the 48-kDa protein, and IFN-beta does so very poorly. Neither IFN-alpha nor IFN-beta has any effect on IFN-gamma-induced myristoylation of the 48-kDa protein. The 48-kDa protein is constitutively myristoylated in murine macrophages that have been activated in vivo by intraperitoneal injection of Corynebacterium parvum, suggesting that it may be an early intermediate in the activation of macrophages.
Insights
Interferon gamma (IFN-gamma) triggers myristoylation of a 48 kDa macrophage protein. This process, potentially linked to macrophage activation, is specific to IFN-gamma.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interferon gamma (IFN-gamma) is a key lymphokine involved in immune responses.
- Macrophage activation is a critical process in cellular immunity.
- Protein modification, such as myristoylation, plays a role in cellular signaling.
Purpose of the Study:
- To investigate the effect of interferon gamma (IFN-gamma) on protein myristoylation in macrophages.
- To characterize the nature of the myristic acid-protein linkage.
- To explore the potential role of this modified protein in macrophage activation.
Main Methods:
- Treatment of macrophages with IFN-gamma and other interferon types (IFN-alpha, IFN-beta).
- Analysis of protein myristoylation using biochemical techniques.
- Assessment of the myristic acid-protein bond stability.
- Observation of myristoylation in macrophages activated in vivo.
Main Results:
- IFN-gamma selectively induces myristoylation of a 48 kDa macrophage protein.
- The myristic acid-protein bond is an amide linkage, resistant to hydroxylamine.
- The effect is dose-dependent (1 U/ml) and time-dependent (maximal at 3-4 hr).
- IFN-alpha and IFN-beta show minimal or no induction of this myristoylation.
- The 48 kDa protein is constitutively myristoylated in macrophages activated by Corynebacterium parvum.
Conclusions:
- IFN-gamma specifically induces the myristoylation of a 48 kDa macrophage protein via an amide bond.
- This IFN-gamma-induced myristoylation is distinct from effects of IFN-alpha and IFN-beta.
- The constitutive myristoylation of this protein in activated macrophages suggests its potential role as an early activation intermediate.
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