PMID- 10542222
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras
      and Rap1A.
PG  - 31941-6
AB  - The Eph family of receptor tyrosine kinases has been implicated in many
      developmental patterning processes, including cell segregation, cell migration,
      and axon guidance. The cellular components involved in the signaling pathways of 
      the Eph receptors, however, are incompletely characterized. Using a yeast
      two-hybrid screen, we have identified a novel signaling intermediate, SHEP1 (SH2 
      domain-containing Eph receptor-binding protein 1), which is expressed in the
      embryonic and adult brain. SHEP1 contains an Src homology 2 domain that binds to 
      a conserved tyrosine-phosphorylated motif in the juxtamembrane region of the
      EphB2 receptor and may itself be a target of EphB2 kinase activity, since it
      becomes heavily tyrosine-phosphorylated in cells expressing activated EphB2.
      SHEP1 also contains a domain similar to Ras guanine nucleotide exchange factor
      domains and binds to the GTPases R-Ras and Rap1A, but not Ha-Ras or RalA. Thus,
      SHEP1 directly links activated, tyrosine-phosphorylated Eph receptors to small
      Ras superfamily GTPases.
FAU - Dodelet, V C
AU  - Dodelet VC
AD  - Burnham Institute, La Jolla, California 92037, USA.
FAU - Pazzagli, C
AU  - Pazzagli C
FAU - Zisch, A H
AU  - Zisch AH
FAU - Hauser, C A
AU  - Hauser CA
FAU - Pasquale, E B
AU  - Pasquale EB
LA  - eng
SI  - GENBANK/AF168364
GR  - HD25938/HD/NICHD NIH HHS/United States
GR  - HD26351/HD/NICHD 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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Sh2d3c protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, EphB2)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (RRAS protein, human)
RN  - EC 3.6.1.- (Rras protein, mouse)
RN  - EC 3.6.5.2 (rap1 GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Carrier Proteins/chemistry/*metabolism
MH  - Cell Line
MH  - Cloning, Molecular
MH  - GTP Phosphohydrolases/*metabolism
MH  - Gene Library
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/chemistry/*metabolism
MH  - Polymerase Chain Reaction
MH  - Rabbits
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptor, EphB2
MH  - Signal Transduction
MH  - rap1 GTP-Binding Proteins/*metabolism
MH  - ras Proteins/*metabolism
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.31941 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):31941-6. doi: 10.1074/jbc.274.45.31941.