Disease relevance of SRF

• SRF protein is upregulated during stretch-induced hypertrophy of rooster ALD muscle [1].

High impact information on SRF

• Both SRF and NFAT were also dependent on Rac, Rho, CDC42 and actin [2].
• These data suggest that combinatorial assembly of signaling pathways emanating from the BCR differentially regulate NFAT and SRF, to activate gene expression [2].
• Differential regulation of NFAT and SRF by the B cell receptor via a PLCgamma-Ca(2+)-dependent pathway [2].
• However, SRF responds to lower Ca(2+) and is less dependent on IP(3)R expression than NFAT [2].
• NFAT and SRF are important in the regulation of proliferation and cytokine production in lymphocytes [2].

Biological context of SRF

• Serum response factor (SRF) gene expression in avian embryonic muscle lineages plays a central role in activating alpha-actin gene activity [3].
• During primary myogenesis in culture, SRF transcripts and nuclear SRF protein content increased about 40-fold, as primary myoblasts withdrew from the cell cycle, reaching their highest levels prior to the upregulation of the skeletal alpha-actin gene [3].
• The binding of a nuclear protein complex containing SRF to one of these elements, the MLC box, is required for gene activation and apparently inhibited by other nuclear factors whose binding overlaps that of the SRF complex [4].
• We recently showed that the cardiogenic homeodomain factor, Nkx-2.5, served as a positive acting accessory factor for serum response factor (SRF) and together provided strong transcriptional activation of the cardiac alpha-actin promoter [5].
• In summary, these data point to important roles for rhoA-RhoK signaling in molecular pathways controlling cytoskeletal reorganization, SRF-dependent transcription, and cell survival that are required to produce CoSMCs from proepicardial cells [6].

Anatomical context of SRF

• SRF transcripts appeared in the precardiac splanchnic mesoderm in stage HH 9 embryos and was detected at higher levels in the myocardium, somites, and lateral mesoderm of HH 11 embryos [3].
• In early stage HH 6 avian embryos, SRF mRNA expression showed strong localization to the neural groove, primitive streak, lateral plate mesoderm, and Hensen's node, while distinct SRF expression was seen later in the neural folds and the somites by HH stage 8 [3].
• These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII [7].
• RhoA, a low molecular weight GTPase protein, can regulate cardiac, skeletal, and smooth muscle differentiation through SRF-dependent mechanisms [8].

Associations of SRF with chemical compounds

• Incubation with the selective p160 rho-kinase (p160RhoK) inhibitor Y27632 (RKI) blocked EMT, prevented the appearance of calponin and SMgammaA-positive cells, and abolished expression and nuclear localization of SRF [6].
• This kinase-deleted mutant could partially rescue ERK activation, and interact with multiple tyrosine phosphorylated proteins during antigen receptor signaling, suggesting that ITK uses a scaffolding function that regulates signals leading to specific regulation of SRF activation [9].

Other interactions of SRF

• In addition, one SNP in 5'UTR (C223G) determined the presence or absence of a potential binding site of transcription factor serum response factor (SRF), which might affect the expression of chicken ghrelin gene [10].
• Additionally, stretch-induced alterations in SRF binding to SRE1, from the skeletal alpha-actin promoter, occur regardless of the rate of stretch-induced growth [11].
• These results indicate that the expression of myogenin mRNA and total RNA remains elevated during either slow or maintenance periods of stretch-induced increases in ALD mass, when SRF mRNA has returned to control levels [11].

Analytical, diagnostic and therapeutic context of SRF

• Gel mobility shift assays demonstrated that SRF binding with serum response element 1 of the skeletal alpha-actin promoter had no altered binding patterns from 6-day-stretched Pat nuclear extracts [12].

References