PMID- 12742500
OWN - NLM
STAT- MEDLINE
DCOM- 20031217
LR  - 20211203
IS  - 0041-1345 (Print)
IS  - 0041-1345 (Linking)
VI  - 35
IP  - 3 Suppl
DP  - 2003 May
TI  - Molecular actions of sirolimus: sirolimus and mTor.
PG  - 227S-230S
AB  - Recent therapeutic strategies to combat organ allograft rejection have focused on 
      T-cell signaling pathways and the molecules that comprise them. The macrolide 
      antibiotic produced by the bacterium Streptomyces hygroscopicus, known as 
      sirolimus or rapamycin, has shown great therapeutic potential in the transplant 
      setting. Sirolimus alone or in combination with other immunosuppressive agents 
      can block acute rejection, chronic graft destruction, and promote permanent 
      allograft acceptance. Sirolimus targets a unique serine-threonine kinase, 
      mammalian target of rapamycin (mTor), which plays a key role in mitogenic and 
      nutritional cells signals. Within T cells, mTor regulates a number of proteins 
      likely dependent on T cell growth factors such as interleukin 2. This review is 
      focused on the molecular mechanisms by which mTor may regulate T-cell signaling 
      cascades and affect T-cell responsiveness, and how sirolimus likely uncouples 
      this activity.
FAU - Kirken, R A
AU  - Kirken RA
AD  - Department of Integrative Biology and Pharmacology, The University of Texas 
      Health Science Center at Houston, Houston, Texas 77030, USA. 
      robert.a.kirken@uth.tmc.edu
FAU - Wang, Y L
AU  - Wang YL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Enzyme Activation
MH  - Graft Rejection/*prevention & control
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Signal Transduction/immunology
MH  - Sirolimus/*therapeutic use
MH  - T-Lymphocytes/immunology
MH  - TOR Serine-Threonine Kinases
RF  - 32
EDAT- 2003/05/14 05:00
MHDA- 2003/12/18 05:00
CRDT- 2003/05/14 05:00
PHST- 2003/05/14 05:00 [pubmed]
PHST- 2003/12/18 05:00 [medline]
PHST- 2003/05/14 05:00 [entrez]
AID - S0041134503002306 [pii]
AID - 10.1016/s0041-1345(03)00230-6 [doi]
PST - ppublish
SO  - Transplant Proc. 2003 May;35(3 Suppl):227S-230S. doi: 
      10.1016/s0041-1345(03)00230-6.