Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The assembly of 80S ribosomes requires joining of the 40S and 60S subunits, which is triggered by the formation of an initiation complex on the 40S subunit. This event is rate-limiting for translation, and depends on external stimuli and the status of the cell. Here we show that 60S subunits are activated by release of eIF6 (also termed p27BBP). In the cytoplasm, eIF6 is bound to free 60S but not to 80S. Furthermore, eIF6 interacts in the cytoplasm with RACK1, a receptor for activated protein kinase C (PKC). RACK1 is a major component of translating ribosomes, which harbour significant amounts of PKC. Loading 60S subunits with eIF6 caused a dose-dependent translational block and impairment of 80S formation, which were reversed by expression of RACK1 and stimulation of PKC in vivo and in vitro. PKC stimulation led to eIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational rescue. We propose that eIF6 release regulates subunit joining, and that RACK1 provides a physical and functional link between PKC signalling and ribosome activation.
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PMID:Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly. 1465 45

p27BBP/eIF6 is an evolutionarily conserved regulator of ribosomal function. It is necessary for 60S biogenesis and impedes improper joining of 40S and 60S subunits, regulated by protein kinase C or Efl1p. No data on p27BBP/eIF6 during early development of Metazoa are available. We studied the distribution, post-translational changes and association with the cytoskeleton of p27BBP/ eIF6 during Xenopus oogenesis and early development. Results indicate that p27BBP/eIF6 is present throughout oogenesis, partly associated with 60S subunits, partly free and with little cytoskeleton bound. During prophase I, p27BBP/eIF6 is detected as a single band of 27-kDa. Upon maturation induced by progesterone or protein kinase C, a serine-phosphorylated 29 kDa isoform appears and is kept throughout development to the neurula stage. Confocal microscopy showed that the distribution of p27BBP/eIF6 and its association with the cytoskeleton varies according to oogenesis stages. Briefly, in stage 6 oocytes, p27BBP/eIF6 has a limited dot-like distribution, and does not co-localize with cytokeratin, whereas upon maturation it spreads throughout the cytoplasm. After fertilization, a large fraction coalesces around cytomembranes and a cytochalasin B-sensitive co-localization with cytokeratin occurs. RNAse removes p27BBP/eIF6 from the cytokeratin fibres. Developmental data suggest a role of p27BBP/eIF6 in controlling ribosomal availability or regulating cross-talk between ribosomes and the cytoskeleton.
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PMID:Phosphorylation of p27(BBP)/eIF6 and its association with the cytoskeleton are developmentally regulated in Xenopus oogenesis. 1599 Sep 55

Protein p27BBP/eIF6 is necessary for ribosomal function of all cells. Previous data showed that from mammals to yeast p27BBP/eIF6 is involved in the biogenesis of ribosomal subunit 60S and its association with the 60S prevents premature 80S formation regulated by PKC signaling, indicating that phosphorylation of p27BBP/eIF6 is needed for translation to occur. While in vitro p27BBP/eIF6 is constitutively expressed, and it has a high level of expression in cycling cells, in vivo its expression varies according to tissues and appears regulated by factors up to now unknown. p27BBP/eIF6 has never been investigated in developing organisms where its upregulation can be correlated with tissue growth and differentiation. In this study we have sequenced p27BBP/eIF6 cDNA and studied its expression during development of Xenopus laevis, as the first step for studying its regulation. The amino acid sequence is highly conserved with two putative PKC phosphorylation sites in serine, one site being typical of Xenopus. At the end of gastrulation, the p27BBP/eIF6 riboprobe localizes in the neural plate and in the paraxial mesoderm. In particular, from stage 24, a clear-cut localization occurs in the perspective head. In embryos exposed to teratogens, the localization of p27BBP/eIF6 riboprobe varies according to the change of head size caused by the treatment. p27BBP/eIF6 expression is particularly evident in differentiating olfactory pits, the lens, otic vesicles, and in branchial arches. Features of particular interest are p27BBP/eIF6 high level of expression in the eye field, and in the mid-hindbrain-boundary, two regions with high proliferative activity. Altogether, data indicate that a modulated expression of p27BBP/eIF6 occurs in developing anlagens in addition to a basal level of expression, and may suggest a correlation between p27BBP/eIF6 and proliferative activity. Moreover, the X. laevis cDNA isolation and characterization offer new hints for further studies in relation to potential p27BBP/eIF6 phosphorylation.
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PMID:Expression of p27BBP/eIF6 is highly modulated during Xenopus laevis embryogenesis. 1642 28