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  • 1
    Publication Date: 1991-03-08
    Description: Epidermal growth factor and platelet-derived growth factor can stimulate the production of the second messenger inositol trisphosphate in responsive cells, but the biochemical pathway for these signaling events has been uncertain because the reactions have not been reconstituted with purified molecules in vitro. A reconstitution is described that requires not only the growth factor, its receptor with tyrosine kinase activity, and the soluble phospholipase C-gamma 1, but also the small soluble actin-binding protein profilin. Profilin binds to the substrate phosphatidylinositol 4,5-bisphosphate and inhibits its hydrolysis by unphosphorylated phospholipase C-gamma 1. Phosphorylation of phospholipase C-gamma 1 by the epidermal growth factor receptor tyrosine kinase overcomes the inhibitory effect of profilin and results in an effective activation of phospholipase C-gamma 1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldschmidt-Clermont, P J -- Kim, J W -- Machesky, L M -- Rhee, S G -- Pollard, T D -- GM-26338/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1991 Mar 8;251(4998):1231-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1848725" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Contractile Proteins/metabolism ; Epidermal Growth Factor/*metabolism ; Inositol Phosphates/metabolism ; Isoenzymes/*metabolism ; Kinetics ; Microfilament Proteins/*metabolism ; Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositols/metabolism ; Phosphorylation ; Profilins ; Protein-Tyrosine Kinases/*metabolism ; Receptor, Epidermal Growth Factor/*metabolism ; Signal Transduction ; Type C Phospholipases/*metabolism ; Tyrosine
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1990-03-30
    Description: Profilin is generally thought to regulate actin polymerization, but the observation that acidic phospholipids dissociate the complex of profilin and actin raised the possibility that profilin might also regulate lipid metabolism. Profilin isolated from platelets binds with high affinity to small clusters of phosphatidylinositol 4,5-bisphosphate (PIP2) molecules in micelles and also in bilayers with other phospholipids. The molar ratio of the complex of profilin with PIP2 is 1:7 in micelles of pure PIP2 and 1:5 in bilayers composed largely of other phospholipids. Profilin competes efficiently with platelet cytosolic phosphoinositide-specific phospholipase C for interaction with the PIP2 substrate and thereby inhibits PIP2 hydrolysis by this enzyme. The cellular concentrations and binding characteristics of these molecules are consistent with profilin being a negative regulator of the phosphoinositide signaling pathway in addition to its established function as an inhibitor of actin polymerization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldschmidt-Clermont, P J -- Machesky, L M -- Baldassare, J J -- Pollard, T D -- GM 26338/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 30;247(4950):1575-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2157283" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Chromatography, Gel ; *Contractile Proteins ; Humans ; Hydrolysis ; Micelles ; Microfilament Proteins/*metabolism ; Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositols/*metabolism ; Polymers ; Profilins ; Type C Phospholipases/*antagonists & inhibitors/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 1994-02-15
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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