PMID- 10473609
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 37
DP  - 1999 Sep 10
TI  - SH2-B, a membrane-associated adapter, is phosphorylated on multiple
      serines/threonines in response to nerve growth factor by kinases within the
      MEK/ERK cascade.
PG  - 26485-92
AB  - SH2-B has been shown to be required for nerve growth factor (NGF)-mediated
      neuronal differentiation and survival, associate with NGF receptor TrkA, and be
      tyrosyl-phosphorylated in response to NGF. In this work, we examined whether NGF 
      stimulates phosphorylation of SH2-B on serines/threonines. NGF promotes a
      dramatic upward shift in mobility of SH2-B, resulting in multiple forms that
      cannot be attributed to tyrosyl phosphorylation. Treatment of SH2-B with protein 
      phosphatase 2A, a serine/threonine phosphatase, reduces the many forms to two.
      PD98059, a MEK inhibitor, dramatically inhibits NGF-promoted phosphorylation of
      SH2-B on serines/threonines, whereas depletion of 4beta-phorbol 12-myristate
      13-acetate-sensitive protein kinase Cs does not. ERKs 1 and 2 phosphorylate
      SH2-Bbeta primarily on Ser-96 in vitro. However, NGF still stimulates
      serine/threonine phosphorylation of SH2-Bbeta(S96A). SH2-Bbeta(S96A), like
      wild-type SH2-Bbeta, enhances NGF-induced neurite outgrowth. In contrast,
      SH2-Bbeta(R555E) containing a defective SH2 domain blocks NGF-induced neurite
      outgrowth and displays greatly reduced phosphorylation on serines/threonines in
      response to NGF. SH2-Bbeta(R555E), like wild-type SH2-Bbeta, associates with the 
      plasma membrane, suggesting that the dominant negative effect of SH2-Bbeta(R555E)
      cannot be explained by an abnormal subcellular distribution. In summary, NGF
      stimulates phosphorylation of SH2-B on serines/threonines by kinases downstream
      of MEK, which may be important for NGF-mediated neuronal differentiation and
      survival.
FAU - Rui, L
AU  - Rui L
AD  - Department of Physiology, University of Michigan Medical School, Ann Arbor,
      Michigan 48109-0622, USA.
FAU - Herrington, J
AU  - Herrington J
FAU - Carter-Su, C
AU  - Carter-Su C
LA  - eng
GR  - R01 DK034171/DK/NIDDK NIH HHS/United States
GR  - DK 34171/DK/NIDDK NIH HHS/United States
GR  - P30 CA 46592/CA/NCI NIH HHS/United States
GR  - P60-DK-20572/DK/NIDDK 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 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (SH2B1 protein, rat)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Membrane/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mutagenesis, Site-Directed
MH  - Nerve Growth Factors/*metabolism
MH  - PC12 Cells
MH  - Phosphorylation
MH  - Rats
MH  - Serine/*metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Threonine/*metabolism
EDAT- 1999/09/03 00:00
MHDA- 1999/09/03 00:01
CRDT- 1999/09/03 00:00
PHST- 1999/09/03 00:00 [pubmed]
PHST- 1999/09/03 00:01 [medline]
PHST- 1999/09/03 00:00 [entrez]
AID - 10.1074/jbc.274.37.26485 [doi]
AID - S0021-9258(19)55239-5 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Sep 10;274(37):26485-92. doi: 10.1074/jbc.274.37.26485.