IndraLab
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"For example, gankyrin competes with p16 for binding to CDK4, thus blocking the CDK4-inhibitory activity of p16; p34 SEI1 (SERTAD1) is able to bind to the CDK4-cyclin D1 complex and enhance the latter 's kinase activity; BMI1 (B lymphoma Mo-MLV insertion region 1 homolog, a polycomb ring finger protein) down-regulates the expression of p16 (CDKN2A) and p15 (CDKN2B) genes, which consequently promotes CDK4 mediated phosphorylation of pRb."
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"We found that phorbol ester induces unusually early expression of cyclin D2 in B-1 but not B-2 cells, that this early-expressed cyclin D2 associates with Cdk4, and that this correlates with assembly of active kinase complexes and phosphorylation of Rb at the Cdk4 phosphoacceptor Ser 780 site."
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"Conversely, during cell cycle progression, retinoblastoma protein (pRB) is sequentially phosphorylated by CYCLIN-CDK complexes, and CYCLIN D1-CDK4 specifically phosphorylates pRB on the Ser780 residue, leading to its inactivation and the release of E2F. xref In accordance with our transcriptomic data showing that both CCND1 and CDK4 gene expression were downregulated upon TYRO3 depletion (supplementary table xref ), we observed lower levels of pRB phosphorylation at Ser780 in the three cell lines studied after TYRO3 knockdown, which may, therefore, lead to pRB activation and E2F inactivation, as suggested by IPA analysis of our transcriptomic data (Fig. xref , lower panel)."
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"Sequential phosphorylation of pRb by cyclin dependent kinases including CDK4 regulates S-phase of cells [XREF_BIBR], Cyclin D1 and CDK4 complex phosphorylates pRb at Ser 795 residue to induce DNA synthesis [XREF_BIBR], We directly determined the role of miR-21-regulated cyclin D1 in renal cancer cell proliferation."
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"Phosphorylation of serines 608/612 inhibits binding of E2F-1 to RB. In Nalm-6 acute lymphoblastic leukemia extracts, serine 608 is phosphorylated by CDK4/6 complexes but not by CDK2. We reasoned that phosphorylation of serines 608/612 by redundant CDKs could accelerate phospho group formation and determined which G1 CDK contributes to serine 612 phosphorylation. Here, we report that CDK4 complexes from Nalm-6 extracts phosphorylated in vitro the CDK2-preferred serine 612, which was inhibited by p16INK4a, and fascaplysin. In contrast, serine 780 and serine 795 were efficiently phosphorylated by CDK4 but not by CDK2."
"Phosphorylated by cdk6 and cdk4, and subsequently by cdk2 at ser-567 in g1, thereby releasing e2f1 which is then able to activate cell growth. Here we show that although these cdks phosphorylate multiple residues in prb, they do so with different residue selectivities in vitro;thr821 and thr826 are preferentially phosphorylated by cdk6 and cdk4, respectively."
"By inhibiting selectively either cdk4/6 or cdk2, we show that endogenous D-type cyclins, acting with cdk4/6, are able to phosphorylate pRb only partially, a process that is likely to be completed by cyclin E-cdk2 complexes. Furthermore, cyclin E-cdk2 is unable to phosphorylate pRb in the absence of prior phosphorylation by cyclin D-cdk4/6 complexes."
"By inhibiting selectively either cdk4/6 or cdk2, we show that endogenous D-type cyclins, acting with cdk4/6, are able to phosphorylate pRb only partially, a process that is likely to be completed by cyclin E-cdk2 complexes. Furthermore, cyclin E-cdk2 is unable to phosphorylate pRb in the absence of prior phosphorylation by cyclin D-cdk4/6 complexes."
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"We found that Costello syndrome fibroblasts display elevated level of Rb phosphorylation on serine 780 (Ser (P)-780-Rb) and that pharmacological inhibition of Ras with radicicol, Mek and Erk with PD98059, or cyclin dependent kinase 4 with PD0332991 not only leads to down-regulation of Ser (P)-780-Rb levels but also enhances Rb phosphorylation on threonine 821 (Thr (P)-821-Rb), which coincides with the recovery of elastin production."
"Phosphorylated by cdk6 and cdk4, and subsequently by cdk2 at ser-567 in g1, thereby releasing e2f1 which is then able to activate cell growth. Here we show that although these cdks phosphorylate multiple residues in prb, they do so with different residue selectivities in vitro;thr821 and thr826 are preferentially phosphorylated by cdk6 and cdk4, respectively."
"The pRb phosphorylated in vitro by Cdk4 was inactive as a growth suppressor upon microinjection, but pRb phosphorylated by Cdk2 or Cdk3 retained cell cycle arrest activity. While these kinases efficiently phosphorylate a common set of residues, including S373 and S788, cyclin D1/Cdk4 was a much more efficient kinase for S795 than the other kinases examined."
"The pRb phosphorylated in vitro by Cdk4 was inactive as a growth suppressor upon microinjection, but pRb phosphorylated by Cdk2 or Cdk3 retained cell cycle arrest activity. While these kinases efficiently phosphorylate a common set of residues, including S373 and S788, cyclin D1/Cdk4 was a much more efficient kinase for S795 than the other kinases examined."