PMID- 10751319
OWN - NLM
STAT- MEDLINE
DCOM- 20000427
LR  - 20211203
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 278
IP  - 4
DP  - 2000 Apr
TI  - EGF stimulates gastrin promoter through activation of Sp1 kinase activity.
PG  - C697-708
AB  - Epidermal growth factor (EGF) receptor activation stimulates gastrin gene 
      expression through a GC-rich element called gastrin EGF response element (gERE). 
      This element is bound by Sp1 family members and is a target of the 
      ras-extracellular signal-regulated kinase (Erk) signal transduction cascade. This 
      raised the possibility that Sp1 may be phosphorylated by kinases of this 
      signaling pathway. Erk is capable of phosphorylating other mitogen-inducible 
      transcription factors, e.g., Elk and Sap, suggesting that Erk may also mediate 
      EGF-dependent phosphorylation of Sp1. This possibility was tested by studying 
      Sp1-dependent kinase activity in extracts prepared from EGF-activated AGS cells 
      by use of solid-phase kinase assays and immunoprecipitation of metabolically 
      labeled Sp1. The results revealed that Sp1 kinase activity (like gastrin promoter 
      activation) is inhibited by PD-98059 and, therefore, is dependent on 
      mitogen-activated protein kinase kinase 1 (Mek 1). However, EGF-dependent 
      activation of endogenous Erk did not account for most of the Sp1 kinase activity, 
      since Erk and additional Sp1 kinase activity analyzed in a solid-phase kinase 
      assay eluted from an ion-exchange column in different fractions. Phosphoamino 
      acid analysis of in vivo radiolabeled Sp1 demonstrated that the kinase 
      phosphorylates Sp1 on Ser and Thr in response to EGF. Therefore, most 
      EGF-stimulated Sp1 kinase activity is Mek 1 dependent and distinct from Erk.
FAU - Chupreta, S
AU  - Chupreta S
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 
      48109, USA.
FAU - Du, M
AU  - Du M
FAU - Todisco, A
AU  - Todisco A
FAU - Merchant, J L
AU  - Merchant JL
LA  - eng
GR  - DK02336/DK/NIDDK NIH HHS/United States
GR  - DK34533/DK/NIDDK NIH HHS/United States
GR  - DK45729/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  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Gastrins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Sp1 kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
SB  - IM
MH  - Binding Sites/physiology
MH  - Enzyme Activation/physiology
MH  - Epidermal Growth Factor/*pharmacology
MH  - Gastrins/*genetics
MH  - Humans
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic/*drug effects
MH  - Protein Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2001/02/07 11:00
MHDA- 2001/02/07 11:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/02/07 11:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1152/ajpcell.2000.278.4.C697 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2000 Apr;278(4):C697-708. doi: 
      10.1152/ajpcell.2000.278.4.C697.