Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uncontrolled proliferation of acute myeloid leukemia (AML) cells is an important step during leukemogenesis. However, little is known about the mechanisms leading to growth autonomy. Studies using immortalized murine hematopoietic cell lines have suggested that autocrine production of growth factors, or the constitutive activation of molecules in growth factor signalling pathways, are involved. We have established six spontaneous factor-independent cell lines from the human growth factor-dependent TF-1 cell line. The factor-independent cells showed no detectable growth factor activity. Immunoblotting analyses of tyrosine phosphorylation, Raf-1 and extracellular signal-regulated kinase 2 (ERK-2) showed a similar pattern in all the cell lines including TF-1 cells. Furthermore, somatic-cell hybrids between TF-1 and the factor-independent cells grew in absence of growth factor. Taken together this data demonstrates that the factor independence in this system is dominant and suggests that the molecular event is located either downstream of the Raf-1 and MAP kinases pathway or on an alternative pathway. Finally, the karyotype analysis of one factor-independent cell line TF-1i1 and TF-1H- (G418 resistant, HAT sensitive TF-1 cells) and their hybrids demonstrated an unstable derivative chromosome [der(19) t(19;?) (q13.1;?)] which seemed to correlate with the factor-independence capacity. This model may help in our understanding of autonomous proliferation by human myeloid leukemias.
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PMID:Characterization of spontaneous factor-independent cell lines derived from the human leukemic cell line TF-1: a dominant event. 805 74

Quiescent mammalian fibroblasts can be induced to reenter the cell cycle by growth factors and oncoproteins. We studied the pathway(s) through which v-Src, the oncogenic tyrosine kinase encoded by the v-src oncogene of Rous sarcoma virus, forces serum-starved NIH3T3 cells to enter S-phase. To this purpose, we isolated and characterized a polyclonal population of NIH3T3 cells transformed by the MR31 retroviral vector, encoding G418 resistance and the v-src temperature-sensitive allele from the mutant ts LA31 PR-A. NIH(MR31) cells displayed a temperature-conditional transformed phenotype and could be made quiescent by serum deprivation at the restrictive temperature. Serum stimulation or thermolabile v-Src reactivation induced entry into S-phase to a comparable extent, although with different kinetics. The data suggest that v-Src mitogenic activity involves early activation of the Erk1/Erk2 MAP kinases with very little tyrosine phosphorylation of the Shc adaptor proteins at least during the early stages of v-Src reactivation and that v-Src-induced S-phase entry was strongly inhibited by drugs affecting MEK or PI 3-kinase. Our results also suggest that down-regulation of gas1 gene expression plays an important role in regulating the efficiency of entry into S-phase triggered by reactivated v-Src and that Gas1 down-regulation does not require PI 3-kinase dependent signals.
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PMID:Role of Gas1 down-regulation in mitogenic stimulation of quiescent NIH3T3 cells by v-Src. 979 92

The entire ACTH receptor (ACTH-R) cDNA was amplified by RT/PCR from mouse Y-1 adrenocortical cells, subcloned into the pMOSBlue T vector, sequenced and inserted into the pSVK3 mammalian vector to obtain pSVACTHR. Balb 3T3 fibroblasts were co-transfected with pSVACTHR plus pSV2-neo and the transfectants were selected with G418 and cloned. Genomic integration of pSVACTHR and transcription of ACTH-R cDNA were checked by Southern blot and RT/PCR respectively. Expression of active ACTH-R protein was tested by measuring cAMP production in response to ACTH. Two ACTH-R expressing transfectants (clones 03 and 07) increased cAMP accumulation in response to ACTH. They were morphologically identical to parental 3T3 cells, but required 10-20% FCS to grow. In these transfectants, ACTH induced c-FOS protein expression, but did not activate the ERK isoforms of MAP Kinase and did not stimulate DNA synthesis. Apparently, the ACTH-R in Balb 3T3 cells induces the c-fos gene by a pathway independent of cAMP/protein kinase A and ERK/MAP Kinase.
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PMID:ACTH induces c-fos proto-oncogene in fibroblasts expressing the ACTH receptor. 988 21