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PMID:8262133

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Citation

Leffers, H, Nielsen, MS, Andersen, AH, Honoré, B, Madsen, P, Vandekerckhove, J and Celis, JE (1993) Identification of two human Rho GDP dissociation inhibitor proteins whose overexpression leads to disruption of the actin cytoskeleton. Exp. Cell Res. 209:165-74

Abstract

Proteins (IEF's 1120, 8118, 8120) sharing similarity to the bovine Rho GDP dissociation inhibitor (GDI) have been identified in the human two-dimensional-gel database of keratinocyte proteins. Molecular cloning of the corresponding cDNAs showed that IEF 8118 is the human homolog of bovine GDI while IEF 8120 is a distinct although related protein. All available information indicates the IEF 1120 is a derivative of IEF 8120. The cDNAs coding for IEF's 8118 and 8120 were recombined into vaccinia virus and expressed in differentiated human keratinocytes and their effect on the actin cytoskeleton was assessed by immunofluorescence using TRITC-phalloidin. The results showed that overexpression of both GDI proteins leads to rounding up of the cells and loss of stress fibers and focal contact sites. In addition, the cell to cell adhesion belts gradually disappeared, an effect that was particularly pronounced in infected cells overexpressing IEF 8120. Taken together, the results imply that Rho GDI's play a role in modulating the activity of the Rho proteins as their overexpression mimics phenotypic changes associated with the inactivation of these proteins.

Links

PubMed Online version:10.1006/excr.1993.1298

Keywords

Actins/metabolism; Amino Acid Sequence; Base Sequence; Cloning, Molecular; Cytoskeleton/ultrastructure; DNA, Complementary/genetics; Electrophoresis, Gel, Two-Dimensional; GTP-Binding Proteins/physiology; Gene Expression; Guanine Nucleotide Dissociation Inhibitors; Humans; Isoelectric Point; Keratinocytes/chemistry; Molecular Sequence Data; Molecular Weight; RNA, Messenger/genetics; Recombinant Proteins/metabolism; Recombinant Proteins/pharmacology; Sequence Alignment; Sequence Homology, Amino Acid; rho-Specific Guanine Nucleotide Dissociation Inhibitors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GDIR1

involved_in

GO:2000249: regulation of actin cytoskeleton reorganization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GDIR1

involved_in

GO:0035023: regulation of Rho protein signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GDIR1

involved_in

GO:0007162: negative regulation of cell adhesion

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GDIR1

enables

GO:0005094: Rho GDP-dissociation inhibitor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GDIR2

enables

GO:0005094: Rho GDP-dissociation inhibitor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GDIR2

involved_in

GO:0035023: regulation of Rho protein signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GDIR2

involved_in

GO:2000249: regulation of actin cytoskeleton reorganization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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