PMID- 10202147
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 7
DP  - 1999 Apr 1
TI  - Phosphorylation of Tyr319 in ZAP-70 is required for T-cell antigen
      receptor-dependent phospholipase C-gamma1 and Ras activation.
PG  - 1832-44
AB  - Accumulating evidence indicates that the interdomain B regions of ZAP-70 and Syk 
      play pivotal roles in the coupling of T-cell antigen receptor (TCR) stimulation
      to the activation of downstream signaling pathways. The interdomain B region of
      ZAP-70 contains at least three candidate sites of tyrosine phosphorylation. In
      this report, we identify Tyr319 as a functionally important phosphorylation site 
      in the ZAP-70 interdomain B region. TCR crosslinkage triggered a rapid increase
      in the phosphorylation of Tyr319 in Jurkat T cells. Although mutation of Tyr319
      to Phe had no effect on the tyrosine kinase activity of ZAP-70, the resulting
      ZAP(Y319-->F) mutant failed to reconstitute TCR-dependent Ca2+ mobilization, Ras 
      activation, CD69 expression and NFAT-dependent transcription in ZAP-70-deficient 
      Jurkat cells. These defects were correlated with reduced tyrosine phosphorylation
      of phospholipase C (PLC)-gamma1 and the LAT adapter protein in the
      ZAP(Y319-->F)-expressing cells. On the other hand, ZAP(Y319-->F)-expressing cells
      displayed normal increases in SLP-76 phosphorylation and ERK activation during
      TCR stimulation. Phosphorylation of Tyr319 promoted the association of ZAP-70
      with the SH2 domains of two key signaling molecules, Lck and PLC-gamma1. These
      studies suggest that Tyr319 phosphorylation is required for the assembly of a
      ZAP-70-containing signaling complex that leads to the activation of the
      PLC-gamma1- and Ras-dependent signaling cascades in antigen-stimulated T cells.
FAU - Williams, B L
AU  - Williams BL
AD  - Department of Immunology, Department of Medicine, Mayo Clinic, Rochester, MN
      55905, USA.
FAU - Irvin, B J
AU  - Irvin BJ
FAU - Sutor, S L
AU  - Sutor SL
FAU - Chini, C C
AU  - Chini CC
FAU - Yacyshyn, E
AU  - Yacyshyn E
FAU - Bubeck Wardenburg, J
AU  - Bubeck Wardenburg J
FAU - Dalton, M
AU  - Dalton M
FAU - Chan, A C
AU  - Chan AC
FAU - Abraham, R T
AU  - Abraham RT
LA  - eng
GR  - R01CA74881/CA/NCI NIH HHS/United States
GR  - R01GM47286/GM/NIGMS NIH HHS/United States
GR  - T32AI01763/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (LAT protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (SLP-76 signal Transducing adaptor proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck))
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
RN  - EC 2.7.10.2 (ZAP70 protein, human)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Calcium/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Carrier Proteins/metabolism
MH  - Catalytic Domain/genetics
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - DNA-Binding Proteins/metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Isoenzymes/chemistry/*metabolism
MH  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/chemistry/metabolism
MH  - *Membrane Proteins
MH  - Mitogen-Activated Protein Kinase 1
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - Models, Biological
MH  - NFATC Transcription Factors
MH  - *Nuclear Proteins
MH  - Phospholipase C gamma
MH  - Phosphoproteins/metabolism
MH  - Point Mutation
MH  - Protein-Tyrosine Kinases/chemistry/genetics/*metabolism
MH  - Receptors, Antigen, T-Cell/*metabolism
MH  - Transcription Factors/metabolism
MH  - Type C Phospholipases/chemistry/*metabolism
MH  - ZAP-70 Protein-Tyrosine Kinase
MH  - ras Proteins/*metabolism
MH  - src Homology Domains
PMC - PMC1171269
EDAT- 1999/04/15 00:00
MHDA- 1999/04/15 00:01
CRDT- 1999/04/15 00:00
PHST- 1999/04/15 00:00 [pubmed]
PHST- 1999/04/15 00:01 [medline]
PHST- 1999/04/15 00:00 [entrez]
AID - 10.1093/emboj/18.7.1832 [doi]
PST - ppublish
SO  - EMBO J. 1999 Apr 1;18(7):1832-44. doi: 10.1093/emboj/18.7.1832.