PMID- 10514377
OWN - NLM
STAT- MEDLINE
DCOM- 19991026
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 286
IP  - 5438
DP  - 1999 Oct 8
TI  - The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent
      ubiquitin-protein ligase.
PG  - 309-12
AB  - Ubiquitination of receptor protein-tyrosine kinases (RPTKs) terminates signaling 
      by marking active receptors for degradation. c-Cbl, an adapter protein for RPTKs,
      positively regulates RPTK ubiquitination in a manner dependent on its variant SRC
      homology 2 (SH2) and RING finger domains. Ubiquitin-protein ligases (or E3s) are 
      the components of ubiquitination pathways that recognize target substrates and
      promote their ligation to ubiquitin. The c-Cbl protein acted as an E3 that can
      recognize tyrosine-phosphorylated substrates, such as the activated
      platelet-derived growth factor receptor, through its SH2 domain and that recruits
      and allosterically activates an E2 ubiquitin-conjugating enzyme through its RING 
      domain. These results reveal an SH2-containing protein that functions as a
      ubiquitin-protein ligase and thus provide a distinct mechanism for substrate
      targeting in the ubiquitin system.
FAU - Joazeiro, C A
AU  - Joazeiro CA
AD  - The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, CA
      92037, USA.
FAU - Wing, S S
AU  - Wing SS
FAU - Huang, H
AU  - Huang H
FAU - Leverson, J D
AU  - Leverson JD
FAU - Hunter, T
AU  - Hunter T
FAU - Liu, Y C
AU  - Liu YC
LA  - eng
GR  - CA39780/CA/NCI NIH HHS/United States
GR  - R01 DK56558/DK/NIDDK NIH HHS/United States
GR  - T32CA09523/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Ubiquitins)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)
RN  - EC 2.3.2.23 (ubiquitin-conjugating enzyme UBC4)
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 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
RN  - EC 6.- (Ligases)
RN  - EC 6.3.2.- (CBL protein, human)
SB  - IM
CIN - Science. 1999 Oct 8;286(5438):223, 225. PMID: 10577187
MH  - Amino Acid Sequence
MH  - Cell Line
MH  - Humans
MH  - Ligases/chemistry/*metabolism
MH  - Molecular Sequence Data
MH  - Phosphotyrosine/metabolism
MH  - Point Mutation
MH  - Proto-Oncogene Proteins/chemistry/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-cbl
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptor, Platelet-Derived Growth Factor beta/metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Sequence Alignment
MH  - Signal Transduction
MH  - *Ubiquitin-Conjugating Enzymes
MH  - Ubiquitin-Protein Ligases
MH  - Ubiquitins/*metabolism
MH  - src Homology Domains
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
AID - 7886 [pii]
AID - 10.1126/science.286.5438.309 [doi]
PST - ppublish
SO  - Science. 1999 Oct 8;286(5438):309-12. doi: 10.1126/science.286.5438.309.