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Evidence of sinks and sources in the phospholipase C‐activated PIP 2 cycle
Author(s) -
Suratekar Rohit,
Panda Aniruddha,
Raghu Padinjat,
Krishna Sandeep
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12998
Subject(s) - phosphatidylinositol , microbiology and biotechnology , phospholipase c , signalling , chemistry , mutant , phospholipase , key (lock) , biochemistry , signal transduction , enzyme , biology , ecology , gene
In many eukaryotic signalling cascades, receptor‐mediated phospholipase C ( PLC ) activity triggers phosphatidylinositol‐4,5‐bisphosphate ( PIP 2 ) hydrolysis, leading to information transfer. Coupled with PLC activation is a sequence of reactions spread across multiple compartments which resynthesize PIP 2 , a process essential for supporting sustained PLC signalling. The biochemical strategies coordinating these reactions and, in particular, whether this is a closed cycle with no net addition or loss of metabolites, are poorly understood. Using mathematical models, we find that most closed PIP 2 cycles cannot explain experimentally observed changes in key metabolic intermediates in particular mutants. Thus, we propose that the PIP 2 cycle likely includes at least one metabolic source and one sink whose net activity results in the experimentally observed regulation of this key signalling pathway.