PMID- 10448070
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190607
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 262
IP  - 1
DP  - 1999 Aug 19
TI  - Enhanced phosphatidylinositol 3-kinase activity and high phosphorylation state of
      its downstream signalling molecules mediated by ret with the MEN 2B mutation.
PG  - 68-75
AB  - We compared the intracellular signalling pathways through Ret tyrosine kinase
      activated by glial cell line-derived neurotrophic factor (GDNF), multiple
      endocrine neoplasia (MEN) 2A, or MEN 2B mutation. Tyrosine phosphorylation of
      Grb2-associated binder-1 (Gab1) and activation of phosphatidylinositol 3-kinase
      (PI 3-kinase) were induced at higher levels by GDNF stimulation or the MEN 2B
      mutation than by the MEN 2A mutation. Tyrosine-phosphorylated Gab1 was a major
      component that interacted with the active PI 3-kinase in vivo. In addition, we
      found that p62Dok and PKB/Akt were phosphorylated in a PI 3-kinase-dependent
      manner and the levels of their phosphorylation were significantly higher in the
      MEN 2B transfectant than in the MEN 2A transfectant. Tyrosine phosphorylation of 
      p62Dok resulted in its complex formation with the Ras GTPase-activating protein
      (RasGAP) and the Nck adaptor protein. These findings thus suggested that high
      levels of activation of PI 3-kinase and of phosphorylation of its downstream
      signalling molecules may be associated with the clinical phenotype of MEN 2B.
CI  - Copyright 1999 Academic Press.
FAU - Murakami, H
AU  - Murakami H
AD  - Department of Pathology, Nagoya University School of Medicine, 65 Tsurumai-cho,
      Showa-ku, Nagoya, 466-8550, Japan.
FAU - Iwashita, T
AU  - Iwashita T
FAU - Asai, N
AU  - Asai N
FAU - Shimono, Y
AU  - Shimono Y
FAU - Iwata, Y
AU  - Iwata Y
FAU - Kawai, K
AU  - Kawai K
FAU - Takahashi, M
AU  - Takahashi M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (DOK1 protein, human)
RN  - 0 (Drosophila Proteins)
RN  - 0 (GAB1 protein, human)
RN  - 0 (GAP-associated protein p62)
RN  - 0 (GDNF protein, human)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors)
RN  - 0 (Nck protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (ras GTPase-Activating Proteins)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Ret protein, Drosophila)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - *DNA-Binding Proteins
MH  - *Drosophila Proteins
MH  - Enzyme Activation/drug effects
MH  - GTPase-Activating Proteins
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Glial Cell Line-Derived Neurotrophic Factor Receptors
MH  - Humans
MH  - Multiple Endocrine Neoplasia Type 2a/genetics
MH  - Multiple Endocrine Neoplasia Type 2b/*genetics
MH  - *Mutation
MH  - *Nerve Growth Factors
MH  - Nerve Tissue Proteins/pharmacology
MH  - Neuroblastoma
MH  - Oncogene Proteins/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Phosphotyrosine/metabolism
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins/genetics/*metabolism/physiology
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-ret
MH  - *RNA-Binding Proteins
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism/physiology
MH  - *Signal Transduction/drug effects
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - ras GTPase-Activating Proteins
EDAT- 1999/08/17 00:00
MHDA- 1999/08/17 00:01
CRDT- 1999/08/17 00:00
PHST- 1999/08/17 00:00 [pubmed]
PHST- 1999/08/17 00:01 [medline]
PHST- 1999/08/17 00:00 [entrez]
AID - 10.1006/bbrc.1999.1186 [doi]
AID - S0006-291X(99)91186-5 [pii]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Aug 19;262(1):68-75. doi:
      10.1006/bbrc.1999.1186.