PMID- 10358045
OWN - NLM
STAT- MEDLINE
DCOM- 19990706
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 24
DP  - 1999 Jun 11
TI  - STAT protein recruitment and activation in c-Kit deletion mutants.
PG  - 16965-72
AB  - Stem cell factor (SCF) and its tyrosine kinase receptor, c-Kit, play a crucial
      role in regulating migration and proliferation of melanoblasts, germ cells, and
      hemopoietic cell progenitors by activating a number of intracellular signaling
      molecules. Here we report that SCF stimulation of myeloid cells or fibroblasts
      ectopically expressing c-Kit induces physical association with and tyrosine
      phosphorylation of three signal transducers and activators of transcription
      (STATs) as follows: STAT1alpha, STAT5A, and STAT5B. Other STAT proteins are not
      recruited upon SCF stimulation. Recruitment of STATs leads to their dimerization,
      nuclear translocation, and binding to specific promoter-responsive elements.
      Whereas STAT1alpha, possibly in the form of homodimers, binds to the
      sis-inducible DNA element, STAT5 proteins, either as STAT5A/STAT5B or
      STAT5/STAT1alpha heterodimers, bind to the prolactin-inducible element of the
      beta-casein promoter. The tyrosine kinase activity of Kit appears essential for
      STAT activation since a kinase-defective mutant lacking a kinase insert domain
      was inactive in STAT signaling. However, another mutant that lacked the
      carboxyl-terminal region retained STAT1alpha activation and nuclear translocation
      but was unable to fully activate STAT5 proteins, although it mediated their
      transient phosphorylation. These results indicate that different intracellular
      domains of c-Kit are involved in activation of the various STAT proteins.
FAU - Brizzi, M F
AU  - Brizzi MF
AD  - Department of Internal Medicine, University of Turin, Turin 10126, Italy.
FAU - Dentelli, P
AU  - Dentelli P
FAU - Rosso, A
AU  - Rosso A
FAU - Yarden, Y
AU  - Yarden Y
FAU - Pegoraro, L
AU  - Pegoraro L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interferon-Stimulated Gene Factor 3)
RN  - 0 (Milk Proteins)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Stem Cell Factor)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (gamma interferon activation factor)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Binding Sites
MH  - Biological Transport
MH  - Bone Marrow Cells/cytology/metabolism
MH  - Cell Compartmentation
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Dimerization
MH  - Interferon-Stimulated Gene Factor 3
MH  - *Milk Proteins
MH  - *Mutation
MH  - Phosphorylation
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-kit/*genetics
MH  - Response Elements
MH  - STAT5 Transcription Factor
MH  - Sequence Deletion
MH  - Signal Transduction
MH  - Stem Cell Factor/*pharmacology
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Tyrosine/metabolism
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1074/jbc.274.24.16965 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 11;274(24):16965-72. doi: 10.1074/jbc.274.24.16965.