Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported that combined treatment with bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-4 (FGF-4) induces cardiogenic events culminating in full cardiac differentiation of non-precardiac mesoderm explanted from stage 6 avian embryos (Lough et al. [1996] Dev. Biol. 178:198-202.). To elucidate the respective functions of BMP and FGF in initiating and maintaining the cardiogenic process, we have used these ectopic cells as a cardiac specification model to ascertain requirements for growth factor specificity and extent of application, as well as induction of cardiac transcription factors. The inability of some BMP isoforms to replace the inductive activity of BMPs-2/4 indicated a specific requirement for this signaling pathway; moreover, neither activin-A nor insulin, which support terminal differentiation of precardiac mesoderm, nor leukocyte inhibitory factor (LIF), which promotes hypertrophy in cardiac myocytes, could replace BMP's cardiogenic activity. A similarly specific requirement for FGF-2/4 signaling was revealed since neither FGF-7, activin-A nor insulin could replace this activity. The effect of both factors was concentration-dependent; maximal incidence of explant differentiation for each occurred at 50 ng/ml. Surprisingly, the majority of explants treated with high BMP levels (250 ng/ml) exhibited a non-cardiac phenotype that was characterized by intense expression of alkaline phosphatase, suggesting differentiation toward an alternative mesodermal phenotype. Experiments to assess the duration of exposure to each factor that was required revealed that while exposure to BMP and FGF during only the initial 30 min of a 48-hr culture period was sufficient to induce cardiogenesis in a significant percentage of explants, 100% incidence of explant differentiation was obtained only when FGF treatment was restricted to the first 30 min and BMP was continuously present during the 48-hr culture period. Treatment with both growth factors was required to induce the cardiac transcription factors cNkx-2.5 and SRF; neither mRNA was induced by BMP or FGF alone. These findings indicate that: (1) specific members of the BMP and FGF families are required to induce cardiogenesis in non-precardiac mesoderm; (2) BMPs-2/4 may function as a morphogen; (3) brief application of both factors can induce cardiogenesis in a modest number of explants whereas (4) 100% incidence of explant differentiation can only be attained by brief FGF treatment combined with continuous BMP treatment and (5) both factors are necessary to induce downstream cardiac transcription factors. These findings are interpreted in terms of these factors' possible roles during cardiac specification and differentiation.
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PMID:Requirement for BMP and FGF signaling during cardiogenic induction in non-precardiac mesoderm is specific, transient, and cooperative. 1084 64

Keratinocyte growth factor (KGF or FGF-7) stimulates alveolar type II cell proliferation, but little is known about the signaling pathways involved. We investigated the role of the ERK (p42/44 mitogen activated protein [MAP] kinase) and phosphatidylinositol 3-OH kinase (PI3 kinase) pathways on alveolar type II cell proliferation and differentiation. Rat type II cells were cultured on tissue culture plastic and Matrigel in the presence or absence of KGF and specific chemical inhibitors PD98059, LY294002, and rapamycin at various concentrations. Proliferation was measured by thymidine incorporation and DNA quantitation, and differentiation was measured by expression of surfactant protein A and alkaline phosphatase. We demonstrate that KGF activates distal effectors of the PI3 kinase pathway, PKB/Akt, and p70S6 kinase, as well as p42/44 MAP kinase proteins. Inhibition of these pathways with PD98059, LY294002, or rapamycin inhibited type II cell proliferation but had no significant effect on differentiation. KGF did not activate the c-Jun kinase or p38 MAP kinase pathways. We conclude that the p42/44 MAP kinase and PI3 kinase pathways are important in regulating alveolar type II cell proliferation in response to KGF.
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PMID:Keratinocyte growth factor stimulates alveolar type II cell proliferation through the extracellular signal-regulated kinase and phosphatidylinositol 3-OH kinase pathways. 1474 97