PMID- 10449731
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 17
DP  - 1999 Aug 17
TI  - Regulation of the Src family tyrosine kinase Blk through E6AP-mediated
      ubiquitination.
PG  - 9557-62
AB  - The Src family of nonreceptor tyrosine kinases are important regulators of a
      variety of cellular processes, including cytoskeletal organization, cell-cell
      contact, and cell-matrix adhesion. Activation of Src family kinases also can
      induce DNA synthesis and cellular proliferation; therefore, tight regulation of
      their kinase activities is important for the cell to maintain proliferative
      control. Posttranslational phosphorylation and dephosphorylation are recognized
      as the principle modifications by which the activities of the Src family of
      tyrosine kinases are regulated. We have discovered that this family of kinases
      also is regulated by ubiquitin-mediated proteolysis. Studies aimed at the
      identification of cellular targets for E6AP, an E3 ubiquitin protein ligase
      involved in ubquitin-mediated degradation, led us to the identification of
      members of the Src family kinases as potential substrates for E6AP. We have found
      that E6AP can bind to several of the Src family tyrosine kinases. Here we show
      that activated Blk is preferentially degraded by the ubiquitin-proteasome pathway
      and that its ubiquitination is mediated by E6AP. Identification of members of the
      Src tyrosine kinase family as substrates of the E6AP ubiquitin-protein ligase
      implicates a role for the ubiquitin pathway in regulating the activities of
      individual members of this important family of signaling molecules.
FAU - Oda, H
AU  - Oda H
AD  - Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 
      02115, USA.
FAU - Kumar, S
AU  - Kumar S
FAU - Howley, P M
AU  - Howley PM
LA  - eng
GR  - R01 CA064888/CA/NCI NIH HHS/United States
GR  - R01-CA64888/CA/NCI 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  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Ubiquitins)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.1.- (protein-tyrosine kinase p55(blk))
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - COS Cells
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Enzyme Stability
MH  - Ligases/*metabolism
MH  - Mice
MH  - Transfection
MH  - Ubiquitin-Protein Ligases
MH  - Ubiquitins/*metabolism
MH  - src-Family Kinases/*metabolism
PMC - PMC22247
EDAT- 1999/08/18 00:00
MHDA- 1999/08/18 00:01
CRDT- 1999/08/18 00:00
PHST- 1999/08/18 00:00 [pubmed]
PHST- 1999/08/18 00:01 [medline]
PHST- 1999/08/18 00:00 [entrez]
AID - 10.1073/pnas.96.17.9557 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9557-62. doi:
      10.1073/pnas.96.17.9557.