Linked Life Data

8288587

Source:http://linkedlifedata.com/resource/pubmed/id/8288587

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-2-22
pubmed:abstractText
We have previously found that Raf-1, which is activated by hematopoietic growth factors in association with phosphorylation, is required for hematopoietic cell proliferation. Recently, 12-O-tetradecanoylphorbol 13-acetate has been found to mediate Raf-1 phosphorylation, suggesting that protein kinase C (PKC) may be involved in the Raf-1 activation mechanism(s). Since PKC can be activated by hematopoietic growth factors, it was investigated as a potential "Raf-1 kinase-kinase." Results demonstrate that bryostatin 1, a pharmacologic activator of PKC, induces activation of Raf-1 in FDC-P1 cells. PKC inhibitors H7 and staurosporine block both bryostatin 1- and interleukin-3-mediated Raf-1 phosphorylation and FDC-P1 cell proliferation. Additionally, an antisense c-raf oligodeoxyribonucleotide specifically inhibits bryostatin 1-mediated proliferation, indicating a necessary role for Raf-1 in PKC signaling. Purified PKC can phosphorylate Raf-1 serine residues to high stoichiometry in vitro. Comparative phosphopeptide maps localize two PKC phosphorylation sites to Raf-1 phosphopeptides isolated from hematopoietic growth factor- or bryostatin 1-stimulated cells. The sites of PKC-mediated Raf-1 phosphorylation are deduced to be Ser497 and Ser619. Furthermore, PKC-mediated serine phosphorylation is sufficient to activate the enzymatic function of Raf-1 in vitro. These findings demonstrate that activated PKC can promote hematopoietic cell growth by regulating the enzymatic activity of Raf-1 through direct serine phosphorylation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
269
pubmed:geneSymbol
c-raf-1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1249-56
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8288587-Amino Acid Sequence, pubmed-meshheading:8288587-Bryostatins, pubmed-meshheading:8288587-Cell Division, pubmed-meshheading:8288587-Enzyme Activation, pubmed-meshheading:8288587-Humans, pubmed-meshheading:8288587-Interleukin-3, pubmed-meshheading:8288587-Lactones, pubmed-meshheading:8288587-Macrolides, pubmed-meshheading:8288587-Molecular Sequence Data, pubmed-meshheading:8288587-Oligonucleotides, Antisense, pubmed-meshheading:8288587-Peptide Mapping, pubmed-meshheading:8288587-Peptides, pubmed-meshheading:8288587-Phosphorylation, pubmed-meshheading:8288587-Phosphoserine, pubmed-meshheading:8288587-Protein Kinase C, pubmed-meshheading:8288587-Proto-Oncogene Proteins, pubmed-meshheading:8288587-Proto-Oncogene Proteins c-raf, pubmed-meshheading:8288587-Signal Transduction
pubmed:year
1994
pubmed:articleTitle
Protein kinase C-mediated serine phosphorylation directly activates Raf-1 in murine hematopoietic cells.
pubmed:affiliation
Johns Hopkins Oncology Center, Baltimore, Maryland 21287.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't