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J. Biol. Chem., Vol. 277, Issue 49, 47235-47241, December 6, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/49/47235    most recent M208875200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jacques, K. M. Articles by Randazzo, P. A. Search for Related Content PubMed PubMed Citation Articles by Jacques, K. M. Articles by Randazzo, P. A. Social Bookmarking                      What's this?

Arf1 Dissociates from the Clathrin Adaptor GGA Prior to Being Inactivated by Arf GTPase-activating Proteins^*

Kerry M. Jacques, Zhongzhen Nie, Stacey Stauffer, Dianne S. Hirsch, Ling-Xin Chen, Katherine T. Stanley, and Paul A. Randazzo

From the Laboratory of Cellular Oncology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892

The effectors of monomeric GTP-binding proteins can influence interactions with GTPase-activating proteins (GAPs) in two ways. In one case, effector and GAP binding to the GTP-binding protein is mutually exclusive. In another case, the GTP-binding protein bound to an effector is the substrate for the GTPase-activating protein. Here predictions for these two mechanisms were tested for the Arf1 effector GGA and ASAP family Arf GAPs. GGA inhibited Arf GAP activity of ASAP1, AGAP1, ARAP1, and Arf GAP1 and inhibited binding of Arf1·GTPS to AGAP1 with K_i values correlating with the K_d for the GGA·Arf1 complex. ASAP1 blocked Arf1·GTPS binding to GGA with a K_i similar to the K_d for the ASAP·Arf1·GTPS complex. No interaction of GGA with ASAP1 was detected. Consistent with GGA sequestering Arf from GAPs, overexpression of GGA slowed the rate of Arf dissociation from the Golgi apparatus following treatment with brefeldin A. Mutational analysis revealed the amino-terminal -helix and switch I of Arf1 contributed to interaction with both GGA and GAPs. These data exclude the mechanism previously documented for Arf GAP1/coatomer in which Arf1 is inactivated in a tripartite complex. Instead, termination of Arf1 signals mediated through GGA require that Arf1·GTP dissociates from GGA prior to interaction with GAP and consequent hydrolysis of GTP.

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