PMID- 10366594
OWN - NLM
STAT- MEDLINE
DCOM- 19990712
LR  - 20220309
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 145
IP  - 6
DP  - 1999 Jun 14
TI  - Morphological differentiation of oligodendrocytes requires activation of Fyn
      tyrosine kinase.
PG  - 1209-18
AB  - In the central nervous system, myelination of axons occurs when oligodendrocyte
      progenitors undergo terminal differentiation and initiate process formation and
      axonal ensheathment. Although it is hypothesized that neuron-oligodendrocyte
      contact initiates this process, the molecular signals are not known. Here we find
      that Fyn tyrosine kinase activity is upregulated very early during
      oligodendrocyte progenitor cell differentiation. Concomitant with this increase
      is the appearance of several tyrosine phosphorylated proteins present only in
      differentiated cells. The increased tyrosine kinase activity is specific to Fyn, 
      as other Src family members are not active in oligodendrocytes. To investigate
      the function of Fyn activation on differentiation, we used Src family tyrosine
      kinase inhibitors, PP1 and PP2, in cultures of differentiating oligodendrocyte
      progenitors. Treatment of progenitors with these compounds prevented activation
      of Fyn and reduced process extension and myelin membrane formation. This
      inhibition was reversible and not observed with related inactive analogues. A
      similar effect was observed when a dominant negative Fyn was introduced in
      progenitor cells. These findings strongly suggest that activation of Fyn is an
      essential signaling component for the morphological differentiation of
      oligodendrocytes.
FAU - Osterhout, D J
AU  - Osterhout DJ
AD  - Molecular Neurobiology Program, Skirball Institute, New York University Medical
      Center, New York 10016, USA.
FAU - Wolven, A
AU  - Wolven A
FAU - Wolf, R M
AU  - Wolf RM
FAU - Resh, M D
AU  - Resh MD
FAU - Chao, M V
AU  - Chao MV
LA  - eng
GR  - GM57966/GM/NIGMS 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 Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine)
RN  - 0 (Myelin Proteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - EC 2.7.10.2 (Fyn protein, rat)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - Brain/cytology
MH  - Cell Differentiation/drug effects
MH  - Cell Size/drug effects
MH  - Cells, Cultured
MH  - Enzyme Activation/drug effects
MH  - Fibroblast Growth Factors/pharmacology
MH  - Myelin Proteins/analysis/metabolism
MH  - Myelin Sheath/drug effects/metabolism
MH  - Oligodendroglia/*cytology/drug effects/enzymology/metabolism
MH  - Phosphorylation/drug effects
MH  - Phosphotyrosine/metabolism
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Proto-Oncogene Proteins/analysis/antagonists & inhibitors/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-fyn
MH  - Pyrazoles/pharmacology
MH  - Pyrimidines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stem Cells/*cytology/drug effects/enzymology/metabolism
MH  - *Up-Regulation/drug effects
MH  - src-Family Kinases/antagonists & inhibitors/metabolism
PMC - PMC2133143
EDAT- 1999/06/15 00:00
MHDA- 1999/06/15 00:01
CRDT- 1999/06/15 00:00
PHST- 1999/06/15 00:00 [pubmed]
PHST- 1999/06/15 00:01 [medline]
PHST- 1999/06/15 00:00 [entrez]
AID - 10.1083/jcb.145.6.1209 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Jun 14;145(6):1209-18. doi: 10.1083/jcb.145.6.1209.