Cdc2/Cyclin B1 Interacts with and Modulates Inositol 1,4,5-Trisphosphate Receptor (Type 1) Functions

Li, Xiaogui; Malathi, Krishnamurthy; Križanová, Oľga; Ondriaš, Karol; Sperber, Kirk; Ablamunits, Vitaly; Jayaraman, Thottala

doi:10.4049/jimmunol.175.9.6205

Cited by 35 publications

(15 citation statements)

References 50 publications

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“…The kinase(s) responsible for IP 3 R1 phosphorylation in eggs is not yet known, although it is logical to envisage the participation of MPF and MAPK. Cdc2/cyclin B has already been shown to phosphorylate IP 3 R1 in vitro and in vivo (Li et al, 2005;Malathi et al, 2003). In addition, substratebinding motifs for this kinase were recently reported in IP 3 Rs and, consistent with this, immunoprecipitation studies in breast cancer cells have shown that cyclins and IP 3 R3 can interact (Soghoian et al, 2005).…”

supporting

confidence: 55%

Phosphorylation of IP3R1 and the regulation of[Ca2+]i responses at fertilization: a role for the MAP kinase pathway

et al. 2006

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2+] i ) underlies the initiation of embryo development in most species studied to date. The inositol 1,4,5 trisphosphate receptor type 1 (IP 3 R1) in mammals, or its homologue in other species, is thought to mediate the majority of this Ca 2+ release. IP 3 R1-mediated Ca 2+ release is regulated during oocyte maturation such that it reaches maximal effectiveness at the time of fertilization, which, in mammalian eggs, occurs at the metaphase stage of the second meiosis (MII). Consistent with this, the [Ca 2+ ] i oscillations associated with fertilization in these species occur most prominently during the MII stage. In this study, we have examined the molecular underpinnings of IP 3 R1 function in eggs. Using mouse and Xenopus eggs, we show that IP 3 R1 is phosphorylated during both maturation and the first cell cycle at a MPM2-detectable epitope(s), which is known to be a target of kinases controlling the cell cycle. In vitro phosphorylation studies reveal that MAPK/ERK2, one of the M-phase kinases, phosphorylates IP 3 R1 at at least one highly conserved site, and that its mutation abrogates IP 3 R1 phosphorylation in this domain. Our studies also found that activation of the MAPK/ERK pathway is required for the IP 3 R1 MPM2 reactivity observed in mouse eggs, and that eggs deprived of the MAPK/ERK pathway during maturation fail to mount normal [Ca 2+ ] i oscillations in response to agonists and show compromised IP 3 R1 function. These findings identify IP 3 R1 phosphorylation by M-phase kinases as a regulatory mechanism of IP 3 R1 function in eggs that serves to optimize [Ca 2+ ] i release at fertilization. KEY WORDS: Fertilization, Ca 2+, IP3R1, Mouse, MAPK, Xenopus Development 133, 4355-4365 (2006) Jones and Whittingham, 1996). Given that during maturation and after activation/fertilization the changes in IP 3 R1 concentrations and content of the Ca 2+ stores are small (Brind et al., 2000;Iwasaki et al., 2002;Jellerette et al., 2000), it is likely that other mechanisms might regulate IP 3 R1 function in eggs.Phosphorylation has been shown to be an important regulatory mechanism of IP 3 R1 function (Bezprozvanny, 2005;Patterson et al., 2004a). Among the protein kinases that phosphorylate IP 3 R1 are: protein kinase A and protein kinase C (Ferris et al., 1991;Vermassen et al., 2004a); protein kinase G (Koga et al., 1994); Ca 2+ /calmodulindependent protein kinase II (Ferris et al., 1991;Zhu et al., 1996); the tyrosine kinases Fyn (Jayaraman et al., 1996) and Lyn (Yokoyama et al., 2002); Rho kinase (Singleton and Bourguignon, 2002); and, very recently, protein kinase B (Khan et al., 2006) (V.V., H.D.S. and J.B.P., unpublished). In most cases, IP 3 R1 phosphorylation by these kinases enhances Ca 2+ conductivity, but none of these kinases appears to be intimately associated with cell-cycle transitions. Most importantly, abrogation of their activities by pharmacological inhibitors does not affect IP 3 R1 function in eggs (Carroll and Swann, 1992;Smyth et al., 2002;Swann et al., 1989). However, a ...

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confidence: 55%

Phosphorylation of IP3R1 and the regulation of[Ca2+]i responses at fertilization: a role for the MAP kinase pathway

et al. 2006

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“…Mutagenesis of three residues together (Arg-391, Arg-441, and Arg-871) inhibited binding of the cdc2/CyB complex with the InsP 3 R-1 (252), suggesting they may be involved in interactions between the proteins that enable the phosphorylation of the channel. Functionally, cdc2/CyB-mediated phosphorylation enhanced the affinity of the InsP 3 -binding region for InsP 3 and enhanced InsP 3 -mediated Ca 2ϩ release from microsomes (252,288).…”

Section: Phosphorylation By Cdks/cybmentioning

confidence: 99%

“…The cyclin-dependent kinase 1/cyclin B (cdc2/CyB) complex phosphorylates InsP 3 R-1 at Ser-421 and Thr-799 and InsP 3 R-3 at Ser-795 (252,288). Mutagenesis of three residues together (Arg-391, Arg-441, and Arg-871) inhibited binding of the cdc2/CyB complex with the InsP 3 R-1 (252), suggesting they may be involved in interactions between the proteins that enable the phosphorylation of the channel.…”

Section: Phosphorylation By Cdks/cybmentioning

confidence: 99%

Inositol Trisphosphate Receptor Ca²⁺Release Channels

Foskett

White²,

Cheung³

et al. 2007

Physiological Reviews

1,072

1,334

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The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+ release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca2+ into the cytoplasm in response to InsP3 produced by diverse stimuli, generating complex local and global Ca2+ signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP3R is a calcium-selective cation channel whose gating is regulated not only by InsP3, but by other ligands as well, in particular cytoplasmic Ca2+. Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R.

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“…It has now been shown in somatic cells (a human T cell line) that the type I inositol trisphosphate receptor [Ins(1,4,5)P 3 R] is phosphorylated on two sites by Cdk1, leading to an increase in inositol trisphosphate [Ins (1,4,5)P 3 ] binding (Malathi et al, 2003;Li et al, 2005). This observation may partly explain the Ca 2+ rises that have been recorded during M phase in somatic cells (Ratan et al, 1986;Kao et al, 1990), during early embryogenesis (Groigno and Whitaker, 1998), and during meiotic M phase.…”

Section: Introductionmentioning

confidence: 99%

A novel mechanism controls the Ca2+ oscillations triggered by activation of ascidian eggs and has an absolute requirement for Cdk1 activity

Levasseur

Carroll

Jones

et al. 2007

Journal of Cell Science

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Fertilisation in ascidians triggers a series of periodic rises in cytosolic Ca2+ that are essential for release from metaphase I arrest and progression through meiosis II. These sperm-triggered Ca2+ oscillations are switched off at exit from meiosis II. Ascidian zygotes provided the first demonstration of the positive feedback loop whereby elevated Cdk1 activity maintained these Ca2+ oscillations. Since then it has been reported that Cdk1 sensitises the type I inositol trisphosphate [Ins(1,4,5)P3] receptor in somatic cells, and that sperm-triggered Ca2+ oscillations in mouse zygotes stop because the forming pronuclei sequester phospholipase C zeta that was delivered to the egg by the fertilising sperm. Here, using enucleation, we demonstrate in ascidian eggs that Ca2+ spiking stops at the correct time in the absence of pronuclei. Sequestration of sperm factor is therefore not involved in terminating Ca2+ spiking for these eggs. Instead we found that microinjection of the Cdk1 inhibitor p21 blocked Ca2+ spiking induced by ascidian sperm extract (ASE). However, such eggs were still capable of releasing Ca2+ in response to Ins(1,4,5)P3 receptor agonists, indicating that ASE-triggered Ca2+ oscillations can stop even though the response to Ins(1,4,5)P3 remained elevated. These data suggest that Cdk1 activity promotes Ins(1,4,5)P3 production in the presence of the sperm factor, rather than sensitising the Ca2+ releasing machinery to Ins(1,4,5)P3. These findings suggest a new link between this cell cycle kinase and the Ins(1,4,5)P3 pathway.

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Cdc2/Cyclin B1 Interacts with and Modulates Inositol 1,4,5-Trisphosphate Receptor (Type 1) Functions

Cited by 35 publications

References 50 publications

Phosphorylation of IP3R1 and the regulation of[Ca2+]i responses at fertilization: a role for the MAP kinase pathway

Phosphorylation of IP3R1 and the regulation of[Ca2+]i responses at fertilization: a role for the MAP kinase pathway

Inositol Trisphosphate Receptor Ca²⁺Release Channels

A novel mechanism controls the Ca2+ oscillations triggered by activation of ascidian eggs and has an absolute requirement for Cdk1 activity

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Cdc2/Cyclin B1 Interacts with and Modulates Inositol 1,4,5-Trisphosphate Receptor (Type 1) Functions

Cited by 35 publications

References 50 publications

Phosphorylation of IP3R1 and the regulation of[Ca2+]i responses at fertilization: a role for the MAP kinase pathway

Phosphorylation of IP3R1 and the regulation of[Ca2+]i responses at fertilization: a role for the MAP kinase pathway

Inositol Trisphosphate Receptor Ca2+Release Channels

A novel mechanism controls the Ca2+ oscillations triggered by activation of ascidian eggs and has an absolute requirement for Cdk1 activity

Contact Info

Product

Resources

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Inositol Trisphosphate Receptor Ca²⁺Release Channels