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)

elk-1, an ets related gene codes for a sequence specific DNA binding transcriptional activator which in association with serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE). Recently the C-terminal region of both elk-1 and delta elk-1 proteins was shown to undergo phosphorylation by MAP kinases and function as an activator of MAP kinases. Here we show that delta elk-1 and two other elk-1 related proteins SAP-1a and SAP-1b, like elk-1, can function as transcriptional activators. In this report we have localized the transcriptional activation domain of the SAP-1 proteins (STA) to a large portion of the carboxy terminal region and have identified two autonomous transcriptional activation domains in the elk-1 protein, one at the amino (ETA-1) and the other at the carboxy terminal region (ETA-2). delta elk-1 protein contains only the ETA-2 domain indicating differential usage of activation domains as a result of alternative splicing. We can speculate that the ETA-1 domain can function in vivo independent of ETA-2, but the ETA-2 domain can function either in the absence of ETA-1 (as seen in delta elk-1) or in the presence of accessory proteins like SRF. The role of SRF in the activation of the ternary complex might be to bind to the ETA-1 domain, somehow conceal it's activation domain and in the process unmask the ETA-2 domain (for phosphorylation by MAP kinases) and activate transcription. The ETA-1 domain may be functioning as a negative regulatory transcriptional activation domain for ETA-2. These observations suggest that the elk-1 family of proteins may not only regulate fos and MAP kinases but also other elk-1 target genes that are essential for cellular growth control.
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PMID:Transcriptional activation domains of elk-1, delta elk-1 and SAP-1 proteins. 824 51

We investigated the activation of c-fos transcription following UV irradiation, a 'stress' stimulus. In both HeLa TK- and NIH 3T3 cells the Serum Response Element is required for efficient UV-induced c-fos transcription, and in HeLa TK- cells the Ternary Complex Factor (TCF) binding site contributes substantially to activation. Consistent with this, UV irradiation activates LexA-TCF fusion proteins more strongly in HeLa TK- than in NIH 3T3 cells. The TCF C-termini of the TCFs are substrates for UV-induced MAP kinases: both the Elk-1 and SAP-1a C-termini are efficiently phosphorylated by the p38 MAPK, but only the Elk-1 C-terminus is a good substrate for the SAPK/JNKs. The specificity and activation kinetics of TCF C-terminal kinases, and the susceptibility of transcriptional activation by LexA-TCF fusion proteins to specific inhibitors of different MAPK pathways, show that both the ERK and p38 MAPK pathways contribute to TCF activation in response to UV irradiation. Activity of both these pathways is also required for the response of the c-fos gene itself to UV stimulation.
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PMID:The p38 and ERK MAP kinase pathways cooperate to activate Ternary Complex Factors and c-fos transcription in response to UV light. 897 82

TCFs, which are members of the Ets family of transcription factors, are recruited to the Serum Response Element (SRE) in the c-fos promoter by SRF. These Ets proteins, which are substrates for the MAP kinases, are direct targets of the Ras/MAP kinase signal transduction pathway. In this paper, we demonstrate that one of the TCFs, SAP-1a, displays a significant level of autonomous binding to the SRE Ets box. In contrast to previous observations, deletion of the SRF binding domain did not modulate the autonomous binding of SAP-1a. Also, the autonomous binding was not modulated by the phosphorylation of SAP-1a by MAP kinases. The autonomous binding was also detected in live cells: transfected SAP-1a was able to restore the response of a CArG-less SRE in PC12 cells. The response occurred in the absence of SRF recruitment since a mutant of SAP-1a in which the B-box, a domain required for interaction with SRF, had been deleted was still able to transactivate the CArG-less SRE. The transactivation was repressed by a Ras transdominant negative mutant, indicating the involvement of the Ras/MAP kinase pathway. Taken together, these data demonstrate that SAP-1a is capable of binding to the c-fos SRE in the absence of SRF.
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PMID:Activation of the c-fos SRE through SAP-1a. 934 99