The Journal of pharmacology and experimental therapeuticsMar 13, 1998

How Different Kinases Affect the Trapping of Human Muscarinic Acetylcholine Receptor Subtypes

Circadian Biology Weekly Brief ↗PubMed ↗

Updated Mar 30, 2026

Abstract

Coexpression of G protein-coupled receptor kinases 2 (GRK2) facilitates the sequestration of m2 receptors by enhancing the loss of binding activity.

Sequestration of m2 and m4 receptors in COS-7 cells is facilitated by GRK2 coexpression.
Coexpression of a dominant negative form of GRK2 (DN-GRK2) attenuates m2 and m4 receptor sequestration.
m3 and m5 receptor sequestration is also enhanced by GRK2 coexpression, but not influenced by DN-GRK2.
Coexpression of GRK4 delta, GRK5, and GRK6 shows limited effects on m1-m5 receptor sequestration.
GRK4 delta and GRK5 may contribute to m2 receptor sequestration in BHK-21 cells but do not affect m3 receptors.

Simplified

Sequestration of porcine muscarinic acetylcholine receptor m2 subtypes (m2 receptors) expressed in COS-7 cells is facilitated by coexpression of G protein-coupled receptor kinases 2 (GRK2). We examined the effect of coexpression of GRK2, GRK4 delta, GRK5 and GRK6 on sequestration of human m1-m5 receptors expressed in COS-7 cells, which was assessed as loss of [3H]N-methylscopolamine binding activity from the cell surface. Sequestration of m4 receptors as well as m2 receptors was facilitated by coexpression of GRK2 and attenuated by coexpression of the dominant negative form of GRK2 (DN-GRK2). Sequestration of m3 and m5 receptors also was facilitated by coexpression of GRK2 but not affected by coexpression of DN-GRK2. On the other hand, proportions of sequestered m1 receptors were not significantly different with coexpression of GRK2 and DN-GRK2. GRK4 delta, GRK5 and GRK6 did not facilitate sequestration of m1-m5 receptors in COS-7 cells, except that the sequestration of m2 receptors tended to be facilitated by coexpression of GRK4 delta, GRK5 and GRK6. However, coexpression of GRK4 delta, GRK5, but not GRK6, in BHK-21 cells facilitated sequestration of m2, but not m3, receptors. These results indicate that the effect of GRK2 to facilitate receptor sequestration is not restricted to m2 receptors but is generalized to other muscarinic receptors except m1 receptors and that other kinases, including GRK4 delta, GRK5 and endogenous kinase(s) in COS-7 cells, also contribute to sequestration of m2 and m4 receptors.

How Different Kinases Affect the Trapping of Human Muscarinic Acetylcholine Receptor Subtypes

Abstract

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