Four ARF GAPs in <i>Saccharomyces cerevisiae</i> have both overlapping and distinct functions

Yeast - Tập 20 Số 4 - Trang 315-330 - 2003
Chunjiang Zhang1, J. Bradford Bowzard, Aimee Alexander, Richard Kahn
1Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322-3050, USA

Tóm tắt

AbstractPrevious studies in yeast have revealed the presence of four proteins with a conserved, cysteine‐rich, ARF GAP domain that share the ability to suppress the conditional growth defect of the arf1‐3 mutant. Three of these proteins have been shown previously to be ADP‐ribosylation factor (ARF) GTPase‐activating proteins (GAPs). We now demonstrate that the fourth also exhibits in vitro ARF GAP activity and correlates the suppressor and ARF GAP activities for all four. Because the four ARF GAP proteins are quite diverse outside the ARF GAP domain, a genetic analysis was undertaken to define the level of functional cross‐talk between them. A large number of synthetic defects were observed that point to a high degree of functional overlap among the four ARF GAPs. However, several differences were also noted in the ability of each gene to suppress the synthetic defects of others and in the impact of single or combined deletions on assays of membrane traffic. We interpret these results as supportive evidence for roles of ARF GAPs in a number of distinct, essential cellular processes that include cell growth, protein secretion, endocytosis and cell cycling. The description of the specificities of the ARF GAPs for the different responses is viewed as a necessary first step in dissecting biologically relevant pathways through a functionally overlapping family of signalling proteins. Copyright © 2003 John Wiley & Sons, Ltd.

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