PMID- 10022120
OWN - NLM
STAT- MEDLINE
DCOM- 19990302
LR  - 20171116
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 5
DP  - 1999 Feb 4
TI  - Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor
      stimulation.
PG  - 1147-56
AB  - Cbl-b, a mammalian homolog of Cbl, consists of an N-terminal region (Cbl-b-N)
      highly homologous to oncogenic v-Cbl, a Ring finger, and a C-terminal region
      containing multiple proline-rich stretches and potential tyrosine phosphorylation
      sites. In the present study, we demonstrate that upon engagement of the T cell
      receptor (TCR), endogenous Cbl-b becomes rapidly tyrosine-phosphorylated. In
      heterogeneous COS-1 cells, Cbl-b was phosphorylated on tyrosine residues by both 
      Syk- (Syk/Zap-70) and Src- (Fyn/Lck) family kinases, with Syk kinase inducing the
      most prominent effect. Syk associates and phosphorylates Cbl-b in Jurkat T cells.
      A Tyr-316 Cbl-binding site in Syk was required for the association with and for
      the maximal tyrosine phosphorylation of Cbl-b. Mutation at a loss-of-function
      site (Gly-298) in Cbl-b-N disrupts its interaction with Syk. Cbl-b constitutively
      binds Grb2 and becomes associated with Crk-L upon TCR stimulation. The Grb2- and 
      the Crk-L-binding regions were mapped to the C-terminus of Cbl-b. The
      Crk-L-binding sites were further determined to be Y655DVP and Y709KIP, with the
      latter being the primary binding site. Taken together, these results implicate
      that Cbl-b is involved in TCR-mediated intracellular signaling pathways.
FAU - Elly, C
AU  - Elly C
AD  - Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San
      Diego, California 92121, USA.
FAU - Witte, S
AU  - Witte S
FAU - Zhang, Z
AU  - Zhang Z
FAU - Rosnet, O
AU  - Rosnet O
FAU - Lipkowitz, S
AU  - Lipkowitz S
FAU - Altman, A
AU  - Altman A
FAU - Liu, Y C
AU  - Liu YC
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CD3 Complex)
RN  - 0 (CRKL protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 42HK56048U (Tyrosine)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
RN  - EC 2.7.10.2 (ZAP70 protein, human)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 6.3.2.- (CBL protein, human)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Binding Sites
MH  - CD3 Complex/*metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - Lymphocyte Activation
MH  - Nuclear Proteins/metabolism
MH  - Phosphorylation
MH  - Proline
MH  - Protein Binding
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-cbl
MH  - Receptors, Antigen, T-Cell/*metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes/*metabolism
MH  - Tyrosine
MH  - *Ubiquitin-Protein Ligases
MH  - ZAP-70 Protein-Tyrosine Kinase
MH  - src-Family Kinases/metabolism
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 - 10.1038/sj.onc.1202411 [doi]
PST - ppublish
SO  - Oncogene. 1999 Feb 4;18(5):1147-56. doi: 10.1038/sj.onc.1202411.