CHUL CRCHUQ

Québec, Canada

CHUL CRCHUQ

Québec, Canada
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Fiset A.,CHUL CRCHUQ | Xu E.,CHUL CRCHUQ | Bergeron S.,CHUL CRCHUQ | Marette A.,CHUL CRCHUQ | And 5 more authors.
Cellular Signalling | Year: 2011

The cyclin-dependant kinase Cdk2 is compartmentalized in endosomes but its role is poorly understood. Here we show that Cdk2 present in hepatic endosome fractions is strictly located in a Triton X-100-resistant environment. The endosomal Cdk2 was found to be associated with the protein tyrosine phosphatase SHP-1, a regulator of insulin clearance, and the actin anchor β-catenin, a known substrate for both Cdk2 and SHP-1. In the plasma membranes and endosome fractions, β-catenin is associated with CEACAM1, also known as regulator of insulin clearance. We show that β-catenin, not CEACAM1, is a substrate for Cdk2. Partial down-modulation of Cdk2 in HEK293 cells increased the rate of insulin internalization. These findings reveal that Cdk2 functions, at least in part, via a Cdk2/SHP-1/β-catenin/CEACAM1 axis, and show for the first time that Cdk2 has the capacity to regulate insulin internalization. © 2011 Elsevier Inc.


PubMed | CHUL CRCHUQ
Type: Journal Article | Journal: Cellular signalling | Year: 2011

The cyclin-dependant kinase Cdk2 is compartmentalized in endosomes but its role is poorly understood. Here we show that Cdk2 present in hepatic endosome fractions is strictly located in a Triton X-100-resistant environment. The endosomal Cdk2 was found to be associated with the protein tyrosine phosphatase SHP-1, a regulator of insulin clearance, and the actin anchor -catenin, a known substrate for both Cdk2 and SHP-1. In the plasma membranes and endosome fractions, -catenin is associated with CEACAM1, also known as regulator of insulin clearance. We show that -catenin, not CEACAM1, is a substrate for Cdk2. Partial down-modulation of Cdk2 in HEK293 cells increased the rate of insulin internalization. These findings reveal that Cdk2 functions, at least in part, via a Cdk2/SHP-1/-catenin/CEACAM1 axis, and show for the first time that Cdk2 has the capacity to regulate insulin internalization.

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