PMID- 15836616
OWN - NLM
STAT- MEDLINE
DCOM- 20050603
LR  - 20131121
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 93
IP  - 3
DP  - 2005 May
TI  - Activation of Rac1 by phosphatidylinositol 3-kinase in vivo: role in activation 
      of mitogen-activated protein kinase (MAPK) pathways and retinoic acid-induced 
      neuronal differentiation of SH-SY5Y cells.
PG  - 571-83
AB  - Rho GTPases such as RhoA, Rac1 and Cdc42 are crucial players in the regulation of 
      signal transduction pathways required for neuronal differentiation. Using an in 
      vitro cell culture model of neuroblastoma SH-SY5Y cells, we demonstrated 
      previously that RhoA is an in vivo substrate of tissue transglutaminase (TGase) 
      and retinoic acid (RA) promoted activation of RhoA by transamidation. Although 
      activation of RhoA promoted cytoskeletal rearrangement in SH-SY5Y cells, it was 
      not involved in induction of neurite outgrowth. Here, we demonstrate that RA 
      promotes activation of Rac1 in SH-SY5Y cells in a transamidation-independent 
      manner. RA-induced activation of Rac1 is mediated by phosphatidylinositol 
      3-kinase (PI3K), probably because of phosphorylation of the p85 regulatory 
      subunit by Src kinases. Over-expression of constitutively active PI3K or Rac1-V12 
      induces neurite outgrowth, activation of mitogen activated protein kinases 
      (MAPKs), and expression of neuronal markers. The PI3K inhibitor LY294002, or 
      over-expression of dominant negative Rac1-N17, blocks RA-induced neurite 
      outgrowth, activation of MAPKs, and expression of neuronal markers, suggesting 
      that activation of PI3K/Rac1 signaling represents a potential mechanism for 
      regulation of neuronal differentiation in SH-SY5Y cells.
FAU - Pan, Jing
AU  - Pan J
AD  - Cardiovascular Research Institute, Department of Internal Medicine, The Texas A&M 
      University System Health Science Center, College of Medicine, Temple, Texas 
      76504, USA.
FAU - Kao, Yu-Lin
AU  - Kao YL
FAU - Joshi, Suchitra
AU  - Joshi S
FAU - Jeetendran, Seena
AU  - Jeetendran S
FAU - Dipette, Donald
AU  - Dipette D
FAU - Singh, Ugra S
AU  - Singh US
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Neuropeptides)
RN  - 0 (RAC1 protein, human)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Cell Differentiation/drug effects/*physiology
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects/physiology
MH  - Humans
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Neuropeptides/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Tretinoin/*pharmacology
MH  - rac GTP-Binding Proteins/*metabolism
MH  - rac1 GTP-Binding Protein
EDAT- 2005/04/20 09:00
MHDA- 2005/06/04 09:00
CRDT- 2005/04/20 09:00
PHST- 2005/04/20 09:00 [pubmed]
PHST- 2005/06/04 09:00 [medline]
PHST- 2005/04/20 09:00 [entrez]
AID - JNC3106 [pii]
AID - 10.1111/j.1471-4159.2005.03106.x [doi]
PST - ppublish
SO  - J Neurochem. 2005 May;93(3):571-83. doi: 10.1111/j.1471-4159.2005.03106.x.