PMID- 10509564
OWN - NLM
STAT- MEDLINE
DCOM- 19991027
LR  - 20190718
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 13
IP  - 13
DP  - 1999 Sep 10
TI  - Extracellular HIV-1 Tat protein differentially activates the JNK and ERK/MAPK
      pathways in CD4 T cells.
PG  - 1637-45
AB  - OBJECTIVE: To investigate the intracellular signals elicited by extracellular
      HIV-1 Tat protein in lymphoid CD4 T cells. METHODS: CD4 Jurkat T cells were
      treated with a series of glutathione S-transferase (GST)-Tat fusion proteins:
      full-length two-exon GST-Tat (GST-Tat2E); one-exon Tat, in which the second exon 
      of Tat was deleted (GST-Tat1E); two-exon Tat, in which the seven arginine
      residues have been changed to alanine residues (GST-TatArg(mut)), GST-TatdeltaN, 
      which shows a deletion of the N-terminal 21 amino acids. The cells were either
      treated with soluble GST-Tat proteins or seeded on plates coated with GST-Tat
      proteins immobilized on plastic. At various time points, Jurkat cells were lysed 
      and examined for c-Jun N-terminal kinase (JNK) and extracellular signal-regulated
      kinase/mitogen-activated protein kinase (ERK/MAPK) activity. RESULTS: Soluble and
      immobilized GST-Tat2E, but not GST-Tat1E, GST-TatArg(mut) and GST-TatdeltaN,
      activated JNK in a dose-dependent manner, induced a rapid phosphorylation of
      c-Jun on Ser63 and promoted the de novo synthesis of c-Jun protein. Moreover,
      both GST-Tat2E and GST-Tat1E also stimulated ERK/MAPK. However, the activation of
      JNK was maximal at concentrations of 100 nM of GST-Tat2E and was blocked by the
      S6-kinase inhibitor rapamycin, whereas the activation of ERK/MAPK was already
      maximal at 1 nM of GST-Tat2E and was enhanced by rapamycin. CONCLUSIONS:
      Tat-mediated activation of JNK requires the second exon of Tat, which is
      dispensable for the activation of ERK/MAPK. The ability to stimulate JNK and
      ERK/MAPK does not require Tat internalization.
FAU - Mischiati, C
AU  - Mischiati C
AD  - Department of Morphology and Embryology, University of Ferrara, Italy.
FAU - Pironi, F
AU  - Pironi F
FAU - Milani, D
AU  - Milani D
FAU - Giacca, M
AU  - Giacca M
FAU - Mirandola, P
AU  - Mirandola P
FAU - Capitani, S
AU  - Capitani S
FAU - Zauli, G
AU  - Zauli G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Gene Products, tat)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
SB  - X
MH  - CD4-Positive T-Lymphocytes/*enzymology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Enzyme Inhibitors
MH  - Exons
MH  - Gene Products, tat/genetics/*pharmacology
MH  - Glutathione Transferase/genetics
MH  - *HIV-1
MH  - Humans
MH  - *JNK Mitogen-Activated Protein Kinases
MH  - Jurkat Cells
MH  - MAP Kinase Kinase 4
MH  - MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-jun/biosynthesis
MH  - Sirolimus/pharmacology
MH  - tat Gene Products, Human Immunodeficiency Virus
EDAT- 1999/10/06 00:00
MHDA- 1999/10/06 00:01
CRDT- 1999/10/06 00:00
PHST- 1999/10/06 00:00 [pubmed]
PHST- 1999/10/06 00:01 [medline]
PHST- 1999/10/06 00:00 [entrez]
AID - 10.1097/00002030-199909100-00006 [doi]
PST - ppublish
SO  - AIDS. 1999 Sep 10;13(13):1637-45. doi: 10.1097/00002030-199909100-00006.