PMID- 10026222
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 9
DP  - 1999 Feb 26
TI  - Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of 
      the collagen receptor in platelets.
PG  - 5963-71
AB  - Collagen-related peptide (CRP), a collagen homologue, induces platelet activation
      through a tyrosine kinase-dependent pathway, leading to sequential tyrosine
      phosphorylation of Fc receptor (FcR) gamma-chain, Syk, and phospholipase
      C-gamma2. Here we report that CRP and the platelet low affinity immune receptor
      FcgammaRIIA stimulate tyrosine phosphorylation of the T cell adapter SLP-76,
      whereas the G protein-coupled receptor agonist thrombin induces only minor
      tyrosine phosphorylation. This suggests that SLP-76 has a specific role
      downstream of receptors that signal via an immunoreceptor tyrosine-based
      activation motif. Immunoprecipitation studies demonstrate association of SLP-76
      with SLAP-130, Vav, Fyn, Lyn, and the FcR gamma-chain in CRP-stimulated
      platelets. Several of these proteins, including SLP-76, undergo tyrosine
      phosphorylation in in vitro kinase assays performed on SLP-76 immunoprecipitates.
      Tyrosine phosphorylation of all of these proteins in the in vitro kinase assay
      was abrogated by the Src family kinase inhibitor PP1, suggesting that it is
      mediated by either Fyn or Lyn. The physiological significance of this is
      uncertain, however, since tyrosine phosphorylation of SLP-76 in vivo is not
      altered in either Fyn- or Lyn-deficient platelets. CRP stimulation of
      Syk-deficient platelets demonstrated that in vivo tyrosine phosphorylation of
      SLP-76 is downstream of Syk. The absence of Syk in the SLP-76 immunoprecipitates 
      raises the possibility that another protein is responsible for bringing SLP-76 to
      Syk. Candidates for this include those proteins that co-immunoprecipitate with
      SLP-76, including the FcR gamma-chain. Tyrosine phosphorylation of PLC-gamma2 and
      Ca2+ mobilization is markedly attenuated in SLP-76-deficient platelets following 
      CRP stimulation, suggesting that the adapter plays a critical role in the
      regulation of the phospholipase. The increase in tyrosine phosphorylation of
      SLAP-130 in response to CRP is also inhibited in SLP-76-deficient platelets,
      placing it downstream of SLP-76. This work identifies SLP-76 as an important
      adapter molecule that is regulated by Syk and lies upstream of SLAP-130 and
      PLC-gamma2 in CRP-stimulated platelets.
FAU - Gross, B S
AU  - Gross BS
AD  - Department of Pharmacology, Mansfield Road, Oxford University, Oxford OX1 3QT,
      United Kingdom. barbara.gross@users.jesus.ox.ac.uk
FAU - Lee, J R
AU  - Lee JR
FAU - Clements, J L
AU  - Clements JL
FAU - Turner, M
AU  - Turner M
FAU - Tybulewicz, V L
AU  - Tybulewicz VL
FAU - Findell, P R
AU  - Findell PR
FAU - Koretzky, G A
AU  - Koretzky GA
FAU - Watson, S P
AU  - Watson SP
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 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Enzyme Precursors)
RN  - 0 (Fyb protein, mouse)
RN  - 0 (Integrins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Collagen)
RN  - 0 (SLP-76 signal Transducing adaptor proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (Syk protein, mouse)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Blood Platelets/*metabolism
MH  - Carrier Proteins/metabolism
MH  - Collagen/metabolism
MH  - Enzyme Precursors/*metabolism
MH  - Integrins/*metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, Collagen
MH  - Signal Transduction
MH  - Syk Kinase
MH  - Tyrosine/*metabolism
MH  - src-Family Kinases/metabolism
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - 10.1074/jbc.274.9.5963 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Feb 26;274(9):5963-71. doi: 10.1074/jbc.274.9.5963.