PMID- 10608864
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 53
DP  - 1999 Dec 31
TI  - Activation of the MAPK signal cascade by the neural cell adhesion molecule L1
      requires L1 internalization.
PG  - 37965-73
AB  - L1-mediated axon growth involves intracellular signaling, but the precise
      mechanisms involved are not yet clear. We report a role for the mitogen-activated
      protein kinase (MAPK) cascade in L1 signaling. L1 physically associates with the 
      MAPK cascade components Raf-1, ERK2, and the previously identified p90(rsk) in
      brain. In vitro, ERK2 can phosphorylate L1 at Ser(1204) and Ser(1248) of the L1
      cytoplasmic domain. These two serines are conserved in the L1 family of cell
      adhesion molecules, also being found in neurofascin and NrCAM. The ability of
      ERK2 to phosphorylate L1 suggests that L1 signaling could directly regulate L1
      function by phosphorylation of the L1 cytoplasmic domain. In L1-expressing 3T3
      cells, L1 cross-linking can activate ERK2. Remarkably, the activated ERK
      localizes with endocytosed vesicular L1 rather than cell surface L1, indicating
      that L1 internalization and signaling are coupled. Inhibition of L1
      internalization with dominant-negative dynamin prevents activation of ERK. These 
      results show that L1-generated signals activate the MAPK cascade in a manner most
      likely to be important in regulating L1 intracellular trafficking.
FAU - Schaefer, A W
AU  - Schaefer AW
AD  - Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio
      44106-4975, USA.
FAU - Kamiguchi, H
AU  - Kamiguchi H
FAU - Wong, E V
AU  - Wong EV
FAU - Beach, C M
AU  - Beach CM
FAU - Landreth, G
AU  - Landreth G
FAU - Lemmon, V
AU  - Lemmon V
LA  - eng
GR  - R01 EY005285/EY/NEI 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 (Leukocyte L1 Antigen Complex)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Chick Embryo
MH  - *Endocytosis
MH  - Enzyme Activation
MH  - Leukocyte L1 Antigen Complex
MH  - *MAP Kinase Signaling System
MH  - Membrane Glycoproteins/chemistry/*metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Molecular Sequence Data
MH  - Neural Cell Adhesion Molecules/chemistry/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/metabolism
EDAT- 1999/12/23 00:00
MHDA- 1999/12/23 00:01
CRDT- 1999/12/23 00:00
PHST- 1999/12/23 00:00 [pubmed]
PHST- 1999/12/23 00:01 [medline]
PHST- 1999/12/23 00:00 [entrez]
AID - 10.1074/jbc.274.53.37965 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 31;274(53):37965-73. doi: 10.1074/jbc.274.53.37965.