The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG.

Saris, Christiaan J. M.; Domen, Jos; Berns, Anton

doi:10.1002/j.1460-2075.1991.tb07994.x

Cited by 289 publications

(235 citation statements)

References 52 publications

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“…The pim-1 gene was originally identi®ed as a common locus of retroviral insertion in Moloney murine leukemia virus (MuLV)-induced T cell lymphomas (Selten et al, 1986). The gene encodes a serine/ threonine kinase (Saris et al, 1991;Hoover et al, 1991) and is transcribed primarily in hematopoietic tissues. In addition expression is found in cells with high proliferative activity, e.g.…”

Section: Discussionmentioning

confidence: 99%

Signalling by the oncogenic receptor tyrosine kinase Xmrk leads to activation of STAT5 in Xiphophorus melanoma

et al. 1998

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Overexpression of the mutationally activated Xmrk receptor initiates the formation of hereditary malignant melanoma in the ®sh Xiphophorus. In addition to transcriptional overexpression a cell-type speci®c signal transduction is essential for Xmrk mediated tumor formation. To elucidate the consequence of Xmrk signalling and to identify target proteins that characterize the tumor phenotype, we analysed proteins that are strongly tyrosine phosphorylated in the ®sh melanoma cell line PSM. One of the most prominent phosphotyrosine proteins was found to be the signal transducer and activator of transcription STAT5. In a heterologous cell system (murine pro B-cells), activation of the Xmrk kinase in a chimeric receptor induced tyrosine phosphorylation, nuclear translocation and DNA binding of STAT5. Following receptor stimulation, expression of the STAT5 speci®c target genes cis, osm and pim-1 was induced. In Xiphophorus PSM cells STAT5 was found to be preferentially localized in the nucleus, but treatment with tyrphostin AG555, a speci®c Xmrk kinase-inhibitor, blocked nuclear localization. In these cells as well as in Xiphophorus melanoma expression of pim-1 and constitutive DNA-binding activity of STAT5 was detectable. This constitutive activity was higher in malignant than in benign melanomas, indicating that STAT5 activation is correlated with the malignancy of these tumors.

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Section: Discussionmentioning

confidence: 99%

Signalling by the oncogenic receptor tyrosine kinase Xmrk leads to activation of STAT5 in Xiphophorus melanoma

et al. 1998

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“…First, c-Myc does not contain the substrate recognition sequence for Pim-1 kinase, (Arg/Lys) 3 -X-Ser/Thr-X' (X' is likely neither a basic nor a large hydrophobic residue) (Friedmann et al, 1992). Indeed, according to Saris et al (1991), c-Myc protein was not phosphorylated by Pim-1 in vitro. Second, the coexpression of Pim-1 did not enhance the transcriptional activation of a reporter plasmid by cMyc in transient chloramphenicol acetyl-transferase assays (TM, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that Pim-1 is a protein-serine/ threonine kinase (Telerman et al, 1988;Hoover et al, 1991;Padma and Nagarajan, 1991;Saris et al, 1991). We therefore investigated whether the serine/threonine kinase activity of Pim-1 is required for the stimulation of c-Myc-mediated apoptosis.…”

Section: Pim-1 Stimulates Rather Than Inhibits C-myc-mediated Apoptosismentioning

confidence: 95%

“…For this purpose, we created a kinase-defective Pim-1 mutant (Pim-1K67M) by the conversion of Met at position 67 of the protein into Lys by site-directed mutagenesis. This Pim-1K67M mutant has been shown to lose its intrinsic kinase activity in in vitro kinase assays (Saris et al, 1991;Friedmann et al, 1992). We transfected pcDNA3pim-1K67M expressing this Pim-1 mutant into Rat-1/c-Myc#7 cells and isolated stable transfectants (Rat-1/c-Myc/Pim-1K67M).…”

Section: Pim-1 Stimulates Rather Than Inhibits C-myc-mediated Apoptosismentioning

confidence: 99%

“…The pim-1 cDNA ampli®ed by this primer set is expected to encode only the 34 kDa Pim-1 protein (Saris et al, 1991). Poly(A) + RNA (1 mg) from rat thymus was subjected to reverse transcription, and the product was ampli®ed by PCR using the above primers.…”

Section: Plasmids and Transfectionmentioning

confidence: 99%

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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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Seizure activity induces PIM-1 expression in brain

et al. 1998

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We recently identified KID-1, a previously undescribed protein kinase induced by depolarization in PC12 cells and brain (Feldman et al., 1998). KID-1 shares a high degree of sequence homology with PIM-1, a proto-oncogene previously reported to be expressed in hematopoietic and germ cells. We examined PIM-1 expression in stimulated PC12 cells, brains of kainic acid-treated rats, and a number of tissues from untreated rats. We now report that forskolin, but not depolarization or growth factors, induces PIM-1 expression in PC12 cells. PIM-1 is an immediate early gene induced in response to forskolin stimulation. We detect PIM-1 mRNA in a number of unstimulated tissues and at low levels in unstimulated brain. Systemic kainic acid administration to adult rats induces PIM-1 expression in the dentate gyrus region of the hippocampus.

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The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG.

Cited by 289 publications

References 52 publications

Signalling by the oncogenic receptor tyrosine kinase Xmrk leads to activation of STAT5 in Xiphophorus melanoma

Signalling by the oncogenic receptor tyrosine kinase Xmrk leads to activation of STAT5 in Xiphophorus melanoma

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

Seizure activity induces PIM-1 expression in brain

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