PMID- 10086340
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20181201
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 10
DP  - 1999 Mar 11
TI  - cbl-b inhibits epidermal growth factor receptor signaling.
PG  - 1855-66
AB  - The role of cbl-b in signaling by the epidermal growth factor receptor (EGFR) was
      studied and compared with c-cbl. We demonstrate in vivo, that cbl-b, like c-cbl, 
      is phosphorylated and recruited to the EGFR upon EGF stimulation and both cbl
      proteins can bind to the Grb2 adaptor protein. To investigate the functional role
      of cbl proteins in EGFR signaling, we transfected cbl-b or c-cbl into 32D cells
      overexpressing the EGFR (32D/EGFR). This cell line is absolutely dependent on
      exogenous IL-3 or EGF for sustained growth. 32D/EGFR cells overexpressing cbl-b
      showed markedly inhibited growth in EGF compared to c-cbl transfectants and
      vector controls. This growth inhibition by cbl-b was the result of a dramatic
      increase in the number of cells undergoing apoptosis. Consistent with this
      finding, cbl-b overexpression markedly decreased the amplitude and duration of
      AKT activation upon EGF stimulation compared to either vector controls or c-cbl
      overexpressing cells. In addition, the duration of EGF mediated MAP kinase and
      Jun kinase activation in cells overexpressing cbl-b is shortened. These data
      demonstrate that cbl-b inhibits EGF-induced cell growth and that cbl-b and c-cbl 
      have distinct roles in EGF mediated signaling.
FAU - Ettenberg, S A
AU  - Ettenberg SA
AD  - Genetics Department, Medicine Branch, National Cancer Institute, Bethesda Naval
      Hospital, Maryland 20889, USA.
FAU - Keane, M M
AU  - Keane MM
FAU - Nau, M M
AU  - Nau MM
FAU - Frankel, M
AU  - Frankel M
FAU - Wang, L M
AU  - Wang LM
FAU - Pierce, J H
AU  - Pierce JH
FAU - Lipkowitz, S
AU  - Lipkowitz S
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Proto-Oncogene Proteins)
RN  - 62229-50-9 (Epidermal Growth Factor)
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 (ErbB Receptors)
RN  - EC 6.3.2.- (CBL protein, human)
SB  - IM
MH  - Animals
MH  - Cell Line, Transformed
MH  - Epidermal Growth Factor/metabolism/pharmacology
MH  - ErbB Receptors/*metabolism
MH  - Humans
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-cbl
MH  - Rabbits
MH  - *Signal Transduction
MH  - *Ubiquitin-Protein Ligases
EDAT- 1999/03/23 00:00
MHDA- 1999/03/23 00:01
CRDT- 1999/03/23 00:00
PHST- 1999/03/23 00:00 [pubmed]
PHST- 1999/03/23 00:01 [medline]
PHST- 1999/03/23 00:00 [entrez]
AID - 10.1038/sj.onc.1202499 [doi]
PST - ppublish
SO  - Oncogene. 1999 Mar 11;18(10):1855-66. doi: 10.1038/sj.onc.1202499.