PMID- 26441645
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151007
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 6
DP  - 2015
TI  - The ever unfolding story of cAMP signaling in trypanosomatids: vive la 
      difference!
PG  - 185
LID - 10.3389/fphar.2015.00185 [doi]
LID - 185
AB  - Kinetoplastids are unicellular, eukaryotic, flagellated protozoans containing the 
      eponymous kinetoplast. Within this order, the family of trypanosomatids are 
      responsible for some of the most serious human diseases, including Chagas disease 
      (Trypanosoma cruzi), sleeping sickness (Trypanosoma brucei spp.), and 
      leishmaniasis (Leishmania spp). Although cAMP is produced during the life cycle 
      stages of these parasites, its signaling pathways are very different from those 
      of mammals. The absence of G-protein-coupled receptors, the presence of 
      structurally different adenylyl cyclases, the paucity of known cAMP effector 
      proteins and the stringent need for regulation of cAMP in the small kinetoplastid 
      cells all suggest a significantly different biochemical pathway and likely cell 
      biology. However, each of the main kinetoplastid parasites express four class 
      1-type cyclic nucleotide-specific phosphodiesterases (PDEA-D), which have highly 
      similar catalytic domains to that of human PDEs. To date, only TbrPDEB, expressed 
      as two slightly different isoforms TbrPDEB1 and B2, has been found to be 
      essential when ablated. Although the genomes contain reasonably well conserved 
      genes for catalytic and regulatory domains of protein kinase A, these have been 
      shown to have varied structural and functional roles in the different species. 
      Recent discovery of a role of cAMP/AMP metabolism in a quorum-sensing signaling 
      pathway in T. brucei, and the identification of downstream cAMP Response Proteins 
      (CARPs) whose expression levels correlate with sensitivity to PDE inhibitors, 
      suggests a complex signaling cascade. The interplay between the roles of these 
      novel CARPs and the quorum-sensing signaling pathway on cell division and 
      differentiation makes for intriguing cell biology and a new paradigm in cAMP 
      signal transduction, as well as potential targets for trypanosomatid-specific 
      cAMP pathway-based therapeutics.
FAU - Tagoe, Daniel N A
AU  - Tagoe DN
AD  - Wellcome Trust Centre for Molecular Parasitology, University of Glasgow , 
      Glasgow, UK ; Institute of Infection, Inflammation and Immunity, College of 
      Medical, Veterinary and Life Sciences, University of Glasgow , Glasgow, UK ; 
      Department of Laboratory Technology, Division of Medical Laboratory Technology, 
      University of Cape Coast , Cape Coast, Ghana.
FAU - Kalejaiye, Titilola D
AU  - Kalejaiye TD
AD  - Institute of Infection, Inflammation and Immunity, College of Medical, Veterinary 
      and Life Sciences, University of Glasgow , Glasgow, UK.
FAU - de Koning, Harry P
AU  - de Koning HP
AD  - Institute of Infection, Inflammation and Immunity, College of Medical, Veterinary 
      and Life Sciences, University of Glasgow , Glasgow, UK.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20150907
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC4561360
OTO - NOTNLM
OT  - Leishmania
OT  - PKA
OT  - Trypanosoma brucei
OT  - Trypanosoma cruzi
OT  - adenylyl cyclase
OT  - cAMP
OT  - kinase
OT  - phosphodiesterase
EDAT- 2015/10/07 06:00
MHDA- 2015/10/07 06:01
PMCR- 2015/09/07
CRDT- 2015/10/07 06:00
PHST- 2015/06/16 00:00 [received]
PHST- 2015/08/17 00:00 [accepted]
PHST- 2015/10/07 06:00 [entrez]
PHST- 2015/10/07 06:00 [pubmed]
PHST- 2015/10/07 06:01 [medline]
PHST- 2015/09/07 00:00 [pmc-release]
AID - 10.3389/fphar.2015.00185 [doi]
PST - epublish
SO  - Front Pharmacol. 2015 Sep 7;6:185. doi: 10.3389/fphar.2015.00185. eCollection 
      2015.