Editors' ChoiceCell Biology

ARAP Signaling Nodes

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Science's STKE  29 Jan 2002:
Vol. 2002, Issue 117, pp. tw48
DOI: 10.1126/stke.2002.117.tw48

Changes in cell behavior often involve coordinating multiple intracellular signals. For example, phosphoinositides and the Arf and Rho families of small GTP-binding proteins elicit changes in the cell membrane and cytoskeleton that are associated with cell motility, but it is unclear how these signals are integrated to elicit a specific response. Mirua et al. and Krugmann et al. have identified a family of proteins called ARAPs, named after an unusual domain structure that suggests potential signal integration: an Arf GAP domain, a Rho GAP domain, and five PH domains. ARAP1 was localized to the Golgi complex; ARAP3 was largely cytosolic. Arf GAP activity depended on PtsIns(3,4,5)P3. When overexpressed in cells, ARAP1 induced reorganization of the Golgi complex and stimulated filopodia formation. The RhoGAP domain of ARAP1 induced cell rounding and loss of stress fibers. ARAP3 overexpression caused a reduction in filamentous actin, and it altered the normal lamellipodia and membrane-ruffling response of cells to growth factor treatment. ARAPs may function as nodes in complex signaling networks.

S. Krugmann, K. E. Anderson, S. H. Ridley, N. Risso, A. McGregor, J. Coadwell, K. Davidson, A. Eguinoa, C. D. Ellson, P. Lipp, M. Manifava, N. Kristakis, G. Painter, J. W. Thuring, M. A. Cooper, Z.-Y. Lim, A. B. Holmes, S. K. Dove, R. H. Michell, A. Grewel, A. Nazarian, H. Erjument-Bromage, P. Tempst, L. R. Stephens, P. T. Hawkins, Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices. Mol. Cell 9, 95-108 (2002). [Online Journal]

K. Miura, K. M. Jacques, S. Stauffer, A. Kubosaki, K. Zhu, D. S. Hirsch, J. Resau, Y. Zheng, P. A. Randazzo, ARAP1: A point of convergence for Arf and Rho signalling. Mol. Cell 9, 109-119 (2002). [Online Journal]

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