SmgGDS-607 Regulation of RhoA GTPase Prenylation Is Nucleotide-Dependent

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Splice Variants of SmgGDS Control Small GTPase Prenylation and Membrane Localization*

Ras and Rho small GTPases possessing a C-terminal polybasic region (PBR) are vital signaling proteins whose misregulation can lead to cancer. Signaling by these proteins depends on their ability to bind guanine nucleotides and their prenylation with a geranylgeranyl or farnesyl isoprenoid moiety and subsequent trafficking to cellular membranes. There is little previous evidence that cellular si...

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SmgGDS is a guanine nucleotide exchange factor that specifically activates RhoA and RhoC.

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The SmgGDS splice variant SmgGDS-558 is a key promoter of tumor growth and RhoA signaling in breast cancer.

UNLABELLED Breast cancer malignancy is promoted by the small GTPases RhoA and RhoC. SmgGDS is a guanine nucleotide exchange factor that activates RhoA and RhoC in vitro. We previously reported that two splice variants of SmgGDS, SmgGDS-607, and SmgGDS-558, have different characteristics in binding and transport of small GTPases. To define the role of SmgGDS in breast cancer, we tested the expre...

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RhoA biological activity is dependent on prenylation but independent of specific isoprenoid modification.

Recent studies showed that specific isoprenoid modification may be critical for RhoB subcellular location and function. Therefore, we determined whether the function of the highly related RhoA protein is also critically dependent on specific isoprenoid modification: (a) in contrast to observations with RhoB or Ras proteins, where farnesylated and geranylgeranylated versions showed differences i...

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A new signaling paradigm to control the prenylation and trafficking of small GTPases

Members of the Ras and Rho families of small GTPases regulate diverse signaling pathways that promote normal physiological processes as well as diseases such as cancer. The localization of small GTPases in distinct subcellular regions defines which signaling pathways they activate, thus defining their participation in disease. The plasma membrane is viewed as the region of highest activity for ...

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ژورنال

عنوان ژورنال: Biochemistry

سال: 2018

ISSN: 0006-2960,1520-4995

DOI: 10.1021/acs.biochem.8b00567