LY-GDI, A GDP-DISSOCIATION INHIBITOR OF THE RHOA GTP-BINDING PROTEIN, IS EXPRESSED PREFERENTIALLY IN LYMPHOCYTES

被引:181
作者
SCHERLE, P [1 ]
BEHRENS, T [1 ]
STAUDT, LM [1 ]
机构
[1] NCI,METAB BRANCH,BETHESDA,MD 20892
关键词
RAS-RELATED GTP-BINDING PROTEINS; GDP GTP EXCHANGE INHIBITOR; LYMPHOCYTE ACTIVATION; SUBTRACTIVE HYBRIDIZATION; CDNA;
D O I
10.1073/pnas.90.16.7568
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Ras-related small GTP-binding proteins are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. The interconversion of the active, GTP-bound form of the protein to the inactive, GDP-bound form is influenced by two types of regulatory proteins, those that alter the intrinsic GTPase activity of the GTP-binding protein and those that affect the rate of GDP/GTP exchange. By utilizing a subtractive hybridization approach, we have isolated a human gene encoding Ly-GDI, a protein that has striking homology to the product of a previously cloned gene, Rho-GDI, which inhibits GDP/GTP exchange on the Rho family of GTPases. In contrast to Rho-GDI, which is ubiquitously expressed, Ly-GDI is expressed only in hematopoietic tissues and predominantly in B- and T-lymphocyte cell tines. The full-length Ly-GDI cDNA encodes a 27-kDa protein which binds to RhoA and inhibits GDP dissociation from RhoA. Stimulation of T lymphocytes with phorbol ester leads to phosphorylation of Ly-GDI, suggesting an involvement of Ly-GDI in lymphocyte activation pathways. Cell type-specific regulators of the Ras-like GTP-binding proteins may provide one mechanism by which different cell types respond uniquely to signals transduced through the same cell surface receptor or may provide a way by which the GTP-binding proteins can be uniquely engaged by tissue-restricted receptors.
引用
收藏
页码:7568 / 7572
页数:5
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