PMID- 10022833
OWN - NLM
STAT- MEDLINE
DCOM- 19990426
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 4
DP  - 1999 Feb 15
TI  - Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent
      proliferation.
PG  - 904-15
AB  - We have identified Socs1 as a downstream component of the Kit receptor tyrosine
      kinase signalling pathway. We show that the expression of Socs1 mRNA is rapidly
      increased in primary bone marrow-derived mast cells following exposure to Steel
      factor, and Socs1 inducibly binds to the Kit receptor tyrosine kinase via its Src
      homology 2 (SH2) domain. Previous studies have shown that Socs1 suppresses
      cytokine-mediated differentiation in M1 cells inhibiting Janus family kinases. In
      contrast, constitutive expression of Socs1 suppresses the mitogenic potential of 
      Kit while maintaining Steel factor-dependent cell survival signals. Unlike Janus 
      kinases, Socs1 does not inhibit the catalytic activity of the Kit tyrosine
      kinase. In order to define the mechanism by which Socs1-mediated suppression of
      Kit-dependent mitogenesis occurs, we demonstrate that Socs1 binds to the
      signalling proteins Grb-2 and the Rho-family guanine nucleotide exchange factors 
      Vav. We show that Grb2 binds Socs1 via its SH3 domains to putative diproline
      determinants located in the N-terminus of Socs1, and Socs1 binds to the
      N-terminal regulatory region of Vav. These data suggest that Socs1 is an
      inducible switch which modulates proliferative signals in favour of cell survival
      signals and functions as an adaptor protein in receptor tyrosine kinase
      signalling pathways.
FAU - De Sepulveda, P
AU  - De Sepulveda P
AD  - Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue,
      Toronto M5G 2M9.
FAU - Okkenhaug, K
AU  - Okkenhaug K
FAU - Rose, J L
AU  - Rose JL
FAU - Hawley, R G
AU  - Hawley RG
FAU - Dubreuil, P
AU  - Dubreuil P
FAU - Rottapel, R
AU  - Rottapel R
LA  - eng
SI  - GENBANK/AF120490
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Mitogens)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (RNA, Messenger)
RN  - 0 (Stem Cell Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Carrier Proteins/*genetics/metabolism
MH  - Cell Division
MH  - Cell Survival
MH  - Cytokines/pharmacology
MH  - GRB2 Adaptor Protein
MH  - Gene Expression Regulation/genetics
MH  - Mast Cells
MH  - Mitogens/metabolism
MH  - Oncogene Proteins/metabolism
MH  - Protein Binding
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-kit/metabolism
MH  - Proto-Oncogene Proteins c-vav
MH  - RNA, Messenger/metabolism
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - *Signal Transduction
MH  - Stem Cell Factor/*metabolism
MH  - Vascular Endothelial Growth Factor Receptor-1
MH  - src Homology Domains
PMC - PMC1171183
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - 10.1093/emboj/18.4.904 [doi]
PST - ppublish
SO  - EMBO J. 1999 Feb 15;18(4):904-15. doi: 10.1093/emboj/18.4.904.