Enigmatic relationship of Pleckstrin homology domain with phospholipid breakdown mediated signal transduction.
Research into phospholipid signaling continues to flourish, as more and more bioactive lipids and proteins are being identified and their actions characterised. The Pleckstrin homology (PH) domain is one such newly recognized protein module thought to play an important role in intracellular signal transduction. The tertiary structures of several PH domains have been determined, some of them complexed with ligands and on the basis of structural similarities between PH domains and lipid binding proteins it has been suggested that PH domains may be binding to lipophilic molecules. In fact many of the proteins that contain this domain can interfere with the membrane association. This review examines the specificity of this binding and illustrates the importance of charge-charge interactions in PIP2-PH domain complex formation. The precise physiological functions of PH domain in vivo remains to be explored therefore this review examines the biochemical aspects of the interaction of PH domains with phospholipid breakdown mediated products and proto-oncogenic serine-threonine kinase (Akt), protein tyrosine kinases, which have been found to be a target of phospholipid second messengers. Thus, number of cellular processes mediated by this way, ranging from insulin signaling and protein synthesis to differentiation and cell survival are regulated by this intracellular signaling protein module.
Tyagi
M G
MG
Department of Neuropsycho-Pharmacology & Neurochemistry, Institute of Human Behaviour and Allied Sciences, Jhilmil, Delhi, India.
Bapna
J S
JS
D001798:Blood Proteins / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010750:Phosphoproteins; D015398:Signal Transduction; D018909:src Homology Domains
D001798:Blood Proteins; D010743:Phospholipids; D010750:Phosphoproteins; C039077:platelet protein P47; D010740:Phospholipases