PMID- 10567556
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 12
DP  - 1999 Dec
TI  - Characterization of a novel member of the DOK family that binds and modulates Abl
      signaling.
PG  - 8314-25
AB  - A novel member of the p62(dok) family of proteins, termed DOKL, is described.
      DOKL contains features of intracellular signaling molecules, including an
      N-terminal PH (pleckstrin homology) domain, a central PTB (phosphotyrosine
      binding) domain, and a C-terminal domain with multiple potential tyrosine
      phosphorylation sites and proline-rich regions, which might serve as docking
      sites for SH2- and SH3-containing proteins. The DOKL gene is predominantly
      expressed in bone marrow, spleen, and lung, although low-level expression of the 
      RNA can also be detected in other tissues. DOKL and p62(dok) bind through their
      PTB domains to the Abelson tyrosine kinase in a kinase-dependent manner in both
      yeast and mammalian cells. DOKL is phosphorylated by the Abl tyrosine kinase in
      vivo. In contrast to p62(dok), DOKL lacks YxxP motifs in the C terminus and does 
      not bind to Ras GTPase-activating protein (RasGAP) upon phosphorylation.
      Overexpression of DOKL, but not p62(dok), suppresses v-Abl-induced
      mitogen-activated protein (MAP) kinase activation but has no effect on
      constitutively activated Ras- and epidermal growth factor-induced MAP kinase
      activation. The inhibitory effect requires the PTB domain of DOKL. Finally,
      overexpression of DOKL in NIH 3T3 cells inhibits the transforming activity of
      v-Abl. These results suggest that DOKL may modulate Abl function.
FAU - Cong, F
AU  - Cong F
AD  - Department of Biological Sciences, Columbia University College of Physicians and 
      Surgeons, New York, New York 10032, USA.
FAU - Yuan, B
AU  - Yuan B
FAU - Goff, S P
AU  - Goff SP
LA  - eng
SI  - GENBANK/AF179242
GR  - P01CA75399/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (DOK1 protein, human)
RN  - 0 (Dok1 protein, mouse)
RN  - 0 (GAP-associated protein p62)
RN  - 0 (Oncogene Proteins v-abl)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Line, Transformed
MH  - Cell Transformation, Neoplastic
MH  - DNA, Complementary
MH  - *DNA-Binding Proteins
MH  - Enzyme Activation
MH  - Fusion Proteins, bcr-abl/*metabolism
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Molecular Sequence Data
MH  - Oncogene Proteins v-abl/*metabolism
MH  - Phosphoproteins/classification/genetics/*metabolism
MH  - Phosphorylation
MH  - *RNA-Binding Proteins
MH  - Recombinant Fusion Proteins/metabolism
MH  - Saccharomyces cerevisiae
MH  - Subcellular Fractions
MH  - Tissue Distribution
MH  - Tyrosine/metabolism
PMC - PMC84915
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1128/MCB.19.12.8314 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Dec;19(12):8314-25. doi: 10.1128/MCB.19.12.8314.