Abstract：
:Phospholipase C (PLC) isozymes are directly activated by heterotrimeric G proteins and Ras-like GTPases to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and inositol 1,4,5-trisphosphate. Although PLCs play central roles in myriad signaling cascades, the molecular details of their activation remain poorly understood. As described here, the crystal structure of PLC-beta2 illustrates occlusion of the active site by a loop separating the two halves of the catalytic TIM barrel. Removal of this insertion constitutively activates PLC-beta2 without ablating its capacity to be further stimulated by classical G protein modulators. Similar regulation occurs in other PLC members, and a general mechanism of interfacial activation at membranes is presented that provides a unifying framework for PLC activation by diverse stimuli.
journal_name
Mol Celljournal_title
Molecular cellauthors
Hicks SN,Jezyk MR,Gershburg S,Seifert JP,Harden TK,Sondek Jdoi
10.1016/j.molcel.2008.06.018subject
Has Abstractpub_date
2008-08-08 00:00:00pages
383-94issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(08)00463-2journal_volume
31pub_type
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