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  • Endocytosis of FcgammaRI is regulated by two distinct signalling pathways.

Endocytosis of FcgammaRI is regulated by two distinct signalling pathways.

FEBS letters (2000-11-18)
J C Norman, J M Allen
ABSTRACT

Aggregation by immune complexes of receptors specific for the Fc region of IgG results in their internalisation and disposal by trafficking to lysosomes. We show here that internalisation of FcgammaRI by IFN-gamma treated U937 cells following receptor aggregation by cross-linking antibodies requires the activation of two distinct signalling pathways. The pathways were functionally dissected in streptolysin-O-permeabilised cells by capitalising on their relative dependence on active GTP binding proteins. One pathway required the presence of GTP-gammaS or active betagamma subunits, the other did not. Use of inhibitors revealed that the betagamma-independent pathway required activation of PI 3-kinases and was PKC-independent In contrast, the betagamma-dependent pathway involved activation of phospholipase C-beta and PKC, but was PI 3-kinase-independent. Both these pathways were found to be active in intact cells and are likely to determine receptor trafficking following internalisation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Genistein, Soybean, A cell-permeable, reversible, substrate competitive inhibitor of protein tyrosine kinases, including autophosphorylation of epidermal growth factor receptor kinase (IC₅₀ = 2.6 µM).
Sigma-Aldrich
U-73343, A cell-permeable analog of U-73122 that acts as a very weak inhibitor of phospholipase C. Suitable as a negative control.
Sigma-Aldrich
U-73122, U-73122, CAS 112648-68-7, inhibits agonist-induced phospholipase C activation (IC50 = 1-2.1 µM) in human platelets and neutrophils.