Centaurin-α1 associates with and is phosphorylated by isoforms of protein kinase C

Zemlickova, Eva; Dubois, Thierry; Kerai, Preeti; Clokie, Samuel; Cronshaw, Andy; Wakefield, Robert I.D; Johannes, Franz‐Josef; Aitken, Alastair

doi:10.1016/s0006-291x(03)01187-2

Cited by 25 publications

(23 citation statements)

References 21 publications

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“…Centaurin-α 1 interacts with both CK1α and PKC but is only phosphorylated by PKC (Dubois et al, 2001;Zemlickova et al, 2003) whereas KIF13B is phosphorylated by several unidentified kinases (Hanada et al, 2000). In this respect, it is worth noting here that PtdIns(3,4,5)P 3 , ARF6 and PKC isoforms have been shown to concentrate at the leading edges of the cell surface in order to regulate cell adhesion and migration (Sabe, 2003;Ridley et al, 2003).…”

Section: Discussionmentioning

confidence: 93%

“…Therefore, identification of the binding partners of centaurin-α 1 and their localization within the cell might provide clues to the cellular functions of centaurin-α 1 in vivo. For example, the casein kinase 1α (CK1α) and protein kinase C (PKC) isoforms have recently been shown to interact with centaurin-α 1 ; however, the functional consequences of these interactions have not been fully characterized (Dubois et al, 2001;Zemlickova et al, 2003). In this manuscript, we present evidence that centaurin-α 1 binds to a kinesin motor protein termed KIF13B.…”

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confidence: 97%

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Centaurin-α1 interacts directly with kinesin motor protein KIF13B

Kanamarlapudi

Hanada

Chishti

2005

Journal of Cell Science

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Centaurin-α1 is a phosphatidylinositol 3,4,5-trisphosphate binding protein as well as a GTPase activating protein (GAP) for the ADP-ribosylation factor (ARF) family of small GTPases. To further understand its cellular function, we screened a rat brain cDNA library using centaurin-α1 as bait to identify centaurin-α1 interacting proteins. The yeast two-hybrid screen identified a novel kinesin motor protein as a centaurin-α1 binding partner. The motor protein, termed KIF13B, encoded by a single ∼9.5-kb transcript, is widely expressed with high levels observed in brain and kidney. Yeast two-hybrid and GST pull-down assays showed that the interaction between centaurin-α1 and KIF13B is direct and mediated by the GAP domain of centaurin-α1 and the stalk domain of KIF13B. Centaurin-α1 and KIF13B form a complex in vivo and the KIF13B interaction appears to be specific to centaurin-α1 as other members of the ARF GAP family did not show any binding activity. We also show that KIF13B and centaurin-α1 colocalize at the leading edges of the cell periphery whereas a deletion mutant of centaurin-α1 that lacks the KIF13B binding site, failed to colocalize with KIF13B in vivo. Finally, we demonstrate that KIF13B binding suppresses the ARF6 GAP activity of centaurin-α1 in intact cells. Together, our data suggest a mechanism where direct binding between centaurin-α1 and KIF13B could concentrate centaurin-α1 at the leading edges of cells, thus modulating ARF6 function.

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Section: Discussionmentioning

confidence: 93%

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confidence: 97%

Centaurin-α1 interacts directly with kinesin motor protein KIF13B

Kanamarlapudi

Hanada

Chishti

2005

Journal of Cell Science

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“…The observation that Arf GAPs, such as centaurin ␣1 and ArfGEFs, such as EFA6 and ARNO are potentially regulated by PtdIns(3,4,5)P 3 , and found in dendritic and synaptic regions, lends support to the hypothesis that PI 3-kinase coordinately regulates GEFs and GAPs that control the Arf pathways required for dendritic development. In addition, centaurin ␣1 has multiple identified binding partners in addition to PtdIns(3,4,5)P 3 , including protein kinases and cytoskeletal proteins, which could provide input to centaurin ␣1 regulation from a variety of signaling pathways (Dubois et al, 2001;Dubois et al, 2003;Zemlickova et al, 2003;Thacker et al, 2004;Venkateswarlu et al, 2005;Striker et al, 2006). In turn, centaurin ␣1 may also provide cross-talk to other signaling pathways such as the Ras-MAP kinase pathway, which was shown to be diminished by reducing centaurin ␣1 expression (Hayashi et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

The neuronal Arf GAP centaurin α1 modulates dendritic differentiation

Moore

Thacker

Larimore

et al. 2007

Journal of Cell Science

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ReferencesAggensteiner, M. and Reiser, G. (2003). Expression of the brain-specific membrane adapter protein p42 IP4 /centaurin a, a Ins(1,3,4,5)P 4 /PtdIns(3,4,5)P 3 binding protein, in developing rat brain. Brain Res. Dev. Brain Res. 142,[77][78][79][80][81][82][83][84][85][86][87]. Albertinazzi, C., Za, L., Paris, S. and de Curtis, I. (2003). ADP-ribosylation factor 6 and a functional PIX/p95-APP1 complex are required for Rac1B-mediated neurite outgrowth. Mol. Biol. Cell 14, 1295-1307. Allen, P., Ouimet, C. and Greengard, P. (1997 (1996). Identification and cloning of centaurin alpha: a novel phosphatidylinositol (3,4,5)-trisphosphate binding protein from rat brain.

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“…Intracellular trafficking of p42 IP4 /centaurin a1 might be of biological relevance, because p42 IP4 has a role as an adapter protein, which targets protein partners to places of action. It has already been shown that p42 IP4 /centaurin a1 associates with casein kinase 1 (CK1), nucleolin and protein kinase C (PKC) (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

“…In this linker of approximately 50 amino acids the serine at position 87 has been reported to be one of the phosphorylation sites of protein kinase C isoforms. The second phosphorylation site is the threonine at position 276 located in PHC (38). Therefore, we tested whether phosphorylation of p42 IP4 was essential for EGF-mediated membrane recruitment.…”

Section: Discussionmentioning

confidence: 99%

p42IP4/Centaurin α1, a Brain-specific PtdIns(3,4,5)P3/Ins(1,3,4,5)P4-binding Protein: Membrane Trafficking Induced by Epidermal Growth Factor is Inhibited by Stimulation of Phospholipase C-coupled Thrombin Receptor

et al. 2005

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The brain-specific 42-kDa protein, p42(IP4), contains a N-terminal zinc finger (ZF) motif and a tandem of two pleckstrin homology (PH) domains. p42(IP4) binds in vitro the second messengers phosphatidylinositol(3,4,5)trisphosphate (PtdIns(3,4,5)P3) and inositol(1,3,4,5)tetrakisphosphate (Ins(1,3,4,5)P4). We observed by confocal microscopy in live HEK 293 cells the GFP-p42(IP4), a chimera of human p42(IP4) and green fluorescence protein (GFP). There, we studied the influence of thrombin, which raises Ins(1,3,4,5)P4, on membrane translocation of GFP-p42(IP4), induced by epidermal growth factor (EGF). Thrombin in the presence of LiCl inhibited the EGF-induced membrane recruitment of GFP-p42(IP4). In the absence of LiCl, thrombin weakened the EGF-mediated membrane recruitment of GFP-p42(IP4). Furthermore, the participation of p42(IP4) protein domains on the EGF-mediated membrane translocation was analyzed. We used several p42(IP4) variants, in which one of the domains was deleted. Alternatively, single p42(IP4) domain-GFP fusion proteins were generated. Only the p42(IP4) variant lacking the ZF domain showed a very weak membrane translocation in response to EGF stimulation, but all the other p42(IP4) variants did not translocate. Thus, we conclude that the combination of both PH domains with ZF is required for membrane translocation of p42(IP4).

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Centaurin-α1 associates with and is phosphorylated by isoforms of protein kinase C

Cited by 25 publications

References 21 publications

Centaurin-α1 interacts directly with kinesin motor protein KIF13B

Centaurin-α1 interacts directly with kinesin motor protein KIF13B

The neuronal Arf GAP centaurin α1 modulates dendritic differentiation

p42IP4/Centaurin α1, a Brain-specific PtdIns(3,4,5)P3/Ins(1,3,4,5)P4-binding Protein: Membrane Trafficking Induced by Epidermal Growth Factor is Inhibited by Stimulation of Phospholipase C-coupled Thrombin Receptor

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