Regulation of GRP1-catalyzed ADP Ribosylation Factor Guanine Nucleotide Exchange by Phosphatidylinositol 3,4,5-Trisphosphate

Klarlund, Jes K.; Rameh, Lucia E.; Cantley, Lewis C.; Buxton, Joanne M.; Holik, John; Sakelis, Christoper; Patki, Varsha; Corvera, Silvia; Czech, Michael P.

doi:10.1074/jbc.273.4.1859

Cited by 152 publications

(122 citation statements)

References 28 publications

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“…In addition, Arf proteins are affected by phosphoinositides. Both Arf exchange factors (10,(53)(54)(55)(56) and GAPs (27,28,42) contain PH domains and are activated by phosphoinositides. Thus, PtdInsP 2 could function as a Effect of ASAP1 overexpression on cell spreading rate.…”

Section: Discussionmentioning

confidence: 99%

The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton

Randazzo

Andrade

Miura

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

204

182

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Arf family GTP-binding proteins are best characterized as regulators of membrane traffic, but recent studies indicate an additional role in cytoskeletal organization. An Arf GTPase-activating protein of the centaurin ␤ family, ASAP1 (also known as centaurin ␤4), binds Arf and two other known regulators of the actin cytoskeleton, the tyrosine kinase Src and phosphatidylinositol 4,5-bisphosphate. In this paper, we show that ASAP1 localizes to focal adhesions and cycles with focal adhesion proteins when cells are stimulated to move. Overexpression of ASAP1 altered the morphology of focal adhesions and blocked both cell spreading and formation of dorsal ruffles induced by platelet-derived growth factor (PDGF). On the other hand, ASAP1, with a mutation that disrupted GTPase-activating protein activity, had a reduced effect on cell spreading and increased the number of cells forming dorsal ruffles in response to PDGF. These data support a role for an Arf GTPase-activating protein, ASAP1, as a regulator of cytoskeletal remodeling and raise the possibility that the Arf pathway is a target for PDGF signaling.

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Section: Discussionmentioning

confidence: 99%

The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton

Randazzo

Andrade

Miura

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

204

182

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“…Grp1 exchange activity toward myristoylated Arf1 can be enhanced in vitro by PtdIns-3,4,5-P 3 -containing micelles, suggesting that PtdIns-3,4,5-P 3 regulates Grp1 by recruiting it to membranes where Arf is localized (73).…”

Section: Minireview: Role Of Pi 3-kinase Lipid Products 8348mentioning

confidence: 99%

“…Analysis of its amino acid sequence revealed a PH domain and a Sec7 homology domain. The Grp1 PH domain is very selective for PtdIns-3,4,5-P 3 compared with other phosphoinositides (73). The Sec7 homology domain of Grp1 was shown to function as a guanine nucleotide exchange factor for the small G proteins Arf1 and Arf5.…”

Section: Pi-345-pmentioning

confidence: 99%

The Role of Phosphoinositide 3-Kinase Lipid Products in Cell Function

Rameh

Cantley

1999

Journal of Biological Chemistry

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918

681

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Phosphoinositide 3-kinases 1 are a subfamily of lipid kinases that catalyze the addition of a phosphate molecule specifically to the 3-position of the inositol ring of phosphoinositides. Phosphatidylinositol (PtdIns), the precursor of all phosphoinositides (PI), constitutes less than 10% of the total lipid in eukaryotic cell membranes (Fig. 1). Approximately 5% of cellular PI is phosphorylated at the 4-position (PtdIns-4-P), and another 5% is phosphorylated at both the 4-and 5-positions (PtdIns-4,5-P 2 ). However, less than 0.25% of the total inositol-containing lipids are phosphorylated at the 3-position, consistent with the idea that these lipids exert specific regulatory functions inside the cell, as opposed to a structural function. To date, nine members of the PI 3-K family have been isolated from mammalian cells. They are grouped, as suggested by Domin and Waterfield (1), into three classes according to the molecules that they preferentially utilize as substrates. Four different lipid products can be generated by the different PI 3-K members: the singly phosphorylated form PtdIns-3-P; the doubly phosphorylated forms PtdIns-3,4-P 2 and PtdIns-3,5-P 2 ; and finally the triply phosphorylated form PtdIns-3,4,5-P 3 (Fig. 1).PI 3-K was first described as a PI kinase activity associated with the viral oncoproteins, v-Src, v-Ros, and polyomavirus middle T. Mutational studies of these oncoproteins more than 10 years ago indicated a critical role for the associated PI kinase in cell transformation (reviewed by Ref. 2).Recent advances in the field have been achieved by the development of new techniques to probe for the direct targets of PI 3-K lipid products. The chemical synthesis of short chain fatty acid versions of these lipids (3-5) has been a crucial step in determining the specificity of lipid-binding proteins. Additionally, new cloning strategies have been developed to isolate new lipid-binding proteins (6). Here we will review the most recent advances in our understanding of the role of PI 3-K in cell function by dissecting the contribution of each of its lipid products. PtdIns-3-PRegulation-PtdIns-3-P is constitutively present in both mammalian and yeast cells (7,8). It can be produced in vitro via phosphorylation of PtdIns by Class I, II, or III PI 3-Ks (Fig. 1). However, the majority of PtdIns-3-P in mammalian cells is probably produced by Class III PI 3-K (9). The mammalian Class III enzyme is highly related to the yeast Vps34 gene product (10) and, like the yeast enzyme, is specific for PtdIns and will not phosphorylate PtdIns-4-P or PtdIns-4,5-P 2 (11).Targets-PtdIns-3-P was recently shown to specifically interact with a 70-residue protein module called the FYVE finger domain. This domain is a special type of RING zinc finger that is characterized by two zinc-binding sites and a highly conserved stretch of basic residues surrounding the third zinc-coordinating cysteine. Liposomes containing PtdIns-3-P were shown to associate with several FYVE domains (15)(16)(17). Other phosphoinositides bound poorly ...

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“…A group of proteins has been identified that possess a certain type of pleckstrin homology (PH) domain that interacts specifically with PtdIns-(3,4,5)P $ and, often, its immediate breakdown product, PtdIns(3,4)P # , also thought to be a signalling lipid (reviewed in [2]). These include the serine\threonine-specific protein kinases, protein kinase B (PKB) and 3-phosphoinositide-dependent protein kinase-1 (PDK1) [3], Bruton's tyrosine kinase (BTK) [4], the adaptor proteins DAPP1 (dual adaptor for phosphotyrosine and 3-phosphoinositides) [5,6] and Gab1 [7], as well as the ADPribosylation factor (ARF) GTPase-activating protein (GAP) centaurin-α [8] and the ARF guanine-nucleotide-exchange factor, Grp1 [9,10].…”

Section: Introductionmentioning

confidence: 99%