Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation.

Galaktionov, Konstantin; Jessus, Catherine; Beach, David

doi:10.1101/gad.9.9.1046

Cited by 217 publications

(151 citation statements)

References 93 publications

(118 reference statements)

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“…The link between ras and the cell cycle has been strengthened by more recent reports showing that activated ras induces cyclin D 1 in NIH3T3 cells (Winston et al, 1996;Filmus et al, 1994) and that the raf kinase, a putative downstream target of ras, interacts with and regulates the activity of cdc25 (Galaktionov et al, 1995), a phosphatase involved in regulation of cdc2, an essential G 2 /M kinase. However, the direct roles of ras in regulation of the very complex cell cycle machinery is yet to be elucidated.…”

Section: Introductionmentioning

confidence: 98%

K-ras modulates the cell cycle via both positive and negative regulatory pathways

Fan

Bertino

1997

Oncogene

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Section: Introductionmentioning

confidence: 98%

K-ras modulates the cell cycle via both positive and negative regulatory pathways

Fan

Bertino

1997

Oncogene

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“…It has been suggested that these interactions might link the signal transduction machinery to cell cycle activation (Conklin et al, 1995;Galaktionov et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Alternative splicing of the human CDC25B tyrosine phosphatase. Possible implications for growth control?

et al. 1997

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CDC25B2, a protein tyrosine phosphatase closely related to the putative CDC25B oncogene, was identi®ed in a Burkitt lymphoma cDNA library. CDC25B2 di ers from CDC25B by a 14 residue insertion and a 41 residue deletion, which are both located in the amino-terminal region of the protein, upstream of the catalytic domain. Examination of the genomic sequence revealed that CDC25B1 (formerly B) and CDC25B2 are splice variants of the same gene. A third variant, CDC25B3, that carries both the 14 and the 41 residue sequences was also identi®ed in the same cDNA library. All three variants were detected in a panel of human primary culture and cell lines, although at di erent levels. In primary ®broblasts and in HeLa cells the CDC25B expression is cell cycle regulated, reaching a maximum in G 2 -phase. In vitro, CDC25B1 phosphatase is slightly more active than CDC25B2 and B3. However, episomal overexpression of the three CDC25B variants in ®ssion yeast reveals that in vivo, CDC25B2 is largely more active than either B1 or B3 (B24B34B1) both to complement a thermosensitive S pombe CDC25 activity and to act as a mitotic inducer. Alternative splicing of CDC25B may therefore contribute to the control of cell proliferation.

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“…Since Cdc25A has transforming activity as well (Galaktionov et al, 1995a), Cdc25A may be one of the key molecules that transduce the signal Interestingly, Cdc25A contains a peptide sequence that can be phosphorylated by Pim-1 kinase (TM, unpublished observation). It would therefore be possible that Pim-1 stimulates c-Myc-mediated apoptosis through the phosphorylation and activation of the phosphatase activity of Cdc25A, similar to another serine/threonine kinase, Raf-1, which has been shown to bind and activate the phosphatase activity of Cdc25A (Galaktionov et al, 1995b). We are now performing experiments to test this idea.…”

Section: Discussionmentioning

confidence: 99%

Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation

Mochizuki¹,

Kitanaka²,

Noguchi³

et al. 1997

Oncogene

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Pim-1 oncoprotein is a serine/threonine kinase that can closely cooperate with c-Myc in lymphomagenesis, as does Bcl-2. Although the molecular mechanism of this cooperative transformation remains unknown, it is speculated that, similar to Bcl-2, Pim-1 contributes to transformation by inhibiting apoptosis. In this study, therefore, we examined the e ect of Pim-1 expression on c-Myc-mediated apoptosis of Rat-1 ®broblasts triggered by serum deprivation. Our results showed that, rather than inhibiting apoptosis, Pim-1 expression stimulated cMyc-mediated apoptosis in Rat-1 ®broblasts. Pim-1 stimulated c-Myc-mediated apoptosis through an enhancement of the c-Myc-mediated activation of caspase-3 (CPP32)-like proteases, since the suppression of this activity by a speci®c caspase inhibitor abolished the apoptosis stimulation by Pim-1. A kinase-defective Pim-1 mutant failed to stimulate c-Myc-mediated apoptosis, and Pim-1 expression alone in the absence of c-Myc overexpression did not induce apoptosis of serumdeprived Rat-1 cells, indicating that the kinase activity of Pim-1 and the activated c-Myc signaling pathway were required for apoptosis stimulation by Pim-1. Together, these results suggest that Pim-1 oncoprotein stimulates as a serine/threonine kinase the death signaling elicited by c-Myc at a step upstream of caspase-3-like protease activation in Rat-1 ®broblasts. Our results also suggest that Pim-1 kinase might function cooperatively with c-Myc through the phosphorylation of a factor(s) which regulates the common signaling pathway involved in c-Myc-mediated apoptosis and transformation.

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Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation.

Cited by 217 publications

References 93 publications

K-ras modulates the cell cycle via both positive and negative regulatory pathways

K-ras modulates the cell cycle via both positive and negative regulatory pathways

Alternative splicing of the human CDC25B tyrosine phosphatase. Possible implications for growth control?

Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation

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