Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
23
|
| pubmed:dateCreated |
1995-7-10
|
| pubmed:abstractText |
The c-kit-encoded tyrosine kinase receptor for stem cell factor (Kit/SCFR) is crucial for the development of hematopoietic cells, melanoblasts, and germ cells. Ligand stimulation of Kit/SCFR leads to receptor dimerization and autophosphorylation on tyrosine residues. We recently showed, that protein kinase C (PKC) acts in an SCF-stimulated negative feedback loop, which controls Kit/SCFR tyrosine kinase activity and modulates the cellular responses to SCF (Blume-Jensen, P., Siegbahn, A., Stabel, S., Heldin, C.-H., and Rönnstrand, L. (1993) EMBO J. 12, 4199-4209). We present here the identification of the major phosphorylation sites for PKC in Kit/SCFR. Two serine residues in the kinase insert, Ser-741 and Ser-746, are PKC-dependent phosphorylation sites in vivo and account for all phosphorylation by PKC in vitro. Together they comprise more than 60% of the total SCF-stimulated receptor phosphorylation in living cells and 85-90% of its phosphorylation in resting cells. Two additional serine residues, Ser-821 close to the major tyrosine autophosphorylation site in the kinase domain and Ser-959 in the carboxyl terminus are SCF-stimulated PKC-dependent phosphorylation sites. However, they are not phosphorylated directly by PKC-alpha in vitro. Both specific receptor tyrosine autophosphorylation and specific receptor-associated phosphatidylinositide 3'-kinase activity was increased approximately 2-fold in response to SCF in PAE cells stably expressing Kit/SCFR(S741A/S746A). Furthermore, the kinase activity of Kit/SCFR(S741A/S746A) toward an exogenous substrate was increased, which was reflected as a decreased Km and an increased Vmax, in accordance with the negative regulatory role of PKC on Kit/SCFR signaling.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Hematopoietic Cell Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Polycyclic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-kit,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stem Cell Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/calphostin C
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
9
|
| pubmed:volume |
270
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
14192-200
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:7539802-Base Sequence,
pubmed-meshheading:7539802-Hematopoietic Cell Growth Factors,
pubmed-meshheading:7539802-Molecular Sequence Data,
pubmed-meshheading:7539802-Naphthalenes,
pubmed-meshheading:7539802-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:7539802-Phosphorylation,
pubmed-meshheading:7539802-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:7539802-Polycyclic Compounds,
pubmed-meshheading:7539802-Protein Kinase C,
pubmed-meshheading:7539802-Proto-Oncogene Proteins,
pubmed-meshheading:7539802-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:7539802-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:7539802-Receptors, Colony-Stimulating Factor,
pubmed-meshheading:7539802-Signal Transduction,
pubmed-meshheading:7539802-Stem Cell Factor,
pubmed-meshheading:7539802-Tetradecanoylphorbol Acetate,
pubmed-meshheading:7539802-Transfection
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Identification of the major phosphorylation sites for protein kinase C in kit/stem cell factor receptor in vitro and in intact cells.
|
| pubmed:affiliation |
Ludwig Institute for Cancer Research, Uppsala Branch, Biomedical Center, Sweden.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|