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Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Fibroblast growth factor (FGF) receptors (FGFRs) are structurally related receptor protein tyrosine kinases encoded by four distinct genes. Activation of FGFR-1, -2, and -3 by FGFs induces mitogenic responses in various cell types, but the mitogenic potential of
FGFR-4
has not been previously explored. We have compared the properties of BaF3 murine lymphoid cells and L6 rat myoblast cells engineered to express FGFR-1 or
FGFR-4
. Acidic FGF binds with high affinity to and elicits tyrosine phosphorylation of FGFR-1 or
FGFR-4
receptors displayed on BaF3 cells, but only FGFR-1 activation leads to cell survival and growth.
FGFR-4
activation also fails to elicit detectable signals characteristic of the FGFR-1 response: tyrosine phosphorylation of SHC and extracellular signal-related kinase (ERK) proteins and induction of fos and tis11 RNA expression. The only detected response to
FGFR-4
activation was weak phosphorylation of
phospholipase C
gamma. A chimeric receptor containing the extracellular domain of
FGFR-4
and the intracellular domain of FGFR-1 confers FGF-dependent growth upon transfected BaF3 cells, demonstrating that the intracellular domains of the receptors dictate their functional capacity. Activation of FGFR-1 in transfected L6 myoblasts induced far stronger phosphorylation of
phospholipase C
gamma, SHC, and ERK proteins than could activation of
FGFR-4
in L6 cells, and only FGFR-1 activation induced tyrosine phosphorylation of a characteristic 80-kD protein. Hence, the signaling and biological responses elicited by different FGF receptors substantially differ.
...
PMID:Fibroblast growth factor receptors have different signaling and mitogenic potentials. 826 85
Formation of mesoderm and posterior structures in early Xenopus embryos is dependent on fibroblast growth factor (FGF) signaling. Although several FGF receptors (FGFRs) are expressed in the early embryo, their respective role in these processes remains poorly understood. We provide evidence that FGFR-1 and
FGFR-4
signals elicit distinct responses both in naive and neuralized ectodermal cells. We show that naive ectodermal cells expressing a constitutively active chimeric torso-FGFR-1 (t-R1) are converted into mesoderm in a Ras-dependent manner, while those expressing torso-
FGFR-4
(t-R4) differentiate into epidermis without significant activation of Erk-1. In neuralized ectoderm, expression of t-R4 causes the up-regulation of the midbrain markers En-2 and Wnt-1, but not of the hindbrain nor the spinal cord markers Krox20 and Hoxb9. Mutation of tyr(776) in the
phospholipase C
-(gamma) binding consensus sequence YLDL of t-R4 completely abolishes En-2 and Wnt-1 induction. In contrast to t-R4, platelet derived growth factor (PDGF)-dependent FGFR-1 activation in neuralized ectodermal cells expressing a chimeric PDGFR-FGFR-1 receptor results in the expression of Krox20 and Hoxb9. A similar effect is observed when an inducible form of oncogenic Raf is expressed, therefore implicating FGFR-1 and Raf in the transduction of FGF-caudalizing signals in neural tissue. Our results suggest that FGFR-1 and
FGFR-4
transduce distinct signals in embryonic cells, and mainly differ in their ability to activate the Ras/MAPK pathway.
...
PMID:Signaling specificities of fibroblast growth factor receptors in early Xenopus embryo. 1091 Jul 71
