Principles of Cell Signaling and Biological Consequences
Student #6 Response to Student #4
20 May 2005
Morphine, acts principally on the mu-opioid receptor (MOR), has been shown to influence glucose homeostasis which is mainly regulated by insulin. The studies in this paper examine the mechanism underlying the perturbation resulted from morphine on the insulin receptor (IR) mediated signaling pathways. It showed acute morphine treatment causes 1) serine phosphorylation of the IR and impaired the formation of signaling complex among IR, Shc and Grb2, and 2) serine 612 phosphorylation in IRS-1 resulting in reduced tyrosine phosphorylation YMXM p85-binding motifs, and a weakening in the association of IRS-1/pp85 phosphotidylinositol 3-kinase complex. The latter finding was not observed in chronic treatment. The authors suggested that these interactions are likely to be where crosstalk occurs. These studies provided insights into how morphine, upon binding to its receptor can attenuate the IR signaling and that such interactions may lead to the perturbance in glucose homeostasis observed. This study demonstrates an independent signaling cascade can influence the signaling activities of a second independent pathway in a unidirectional manner.
I agree with the comments of Student#4 in regards to the insights gained from this study in examining the underlying mechanism of how morphine influence IR mediated pathway and that the paper illustrate a unidirectional crosstalk between the two pathways. More experiments are needed to confirm the importance of the interactions observed and their importance in influencing the IR activities in the context of glucose homeostasis. It will also be interesting to further explore why chronic treatment with morphine do not affect the association of IRS-1/Grb2 complex and if there is possibility of IR pathway "overriding" the initial perturbance posed by the acute morphine treatment in chronic treatment.
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882