Lecture Nine: PLC-y1-PKC

This lecture aims to review the variation in the structure and function of the adaptor protein phospholipase C (PLC) family. All PLCs have EF-hand domain, C2 domain, and catalytic X and Y autophosphorylation linkage. Several ligands bind towards these receptors, for instance, hormones, growth factors, external stimuli, and neurotransmitters. The PLC is activated upon binding to the receptor-ligand (EGFR-EGF) complex. The lecture further provides insight into how secondary messengers, inositol triphosphate (IP₃) and diacylglycerol (DAG) activated by PLC. Another protein, phospholipase D (PLD), and how it transduces the signal via protein kinase C (PKC) to elicit cellular response is mentioned. The causes of the dysregulation of the PLC-γ1-PKC pathway and the hallmarks of cancer and its effects are analyzed further by revealing the crosstalk between GPCR and PLC.

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PLC-γ1-PKC pathway

EGFR is an example of a receptor transduced by phospholipase C (PLC-γ1) by binding to EGFR-EGF complexes. PLC then forms two secondary messengers, Diacylglycerol (purple; DAG) and inositol triphosphate (orange-yellow; IP₃) hydrolyzing phosphatidylinositol-4, 5-bisphosphate (PI(4,5)P2) (orange; PIP₂). Diacylglycerol (DAG) activates protein kinase C (peach) and then phosphorylates downstream target cellular proteins for processes, for instance, cell growth, differentiation, and apoptosis. IP₃ then interacts with another second messenger, calcium ions to release into the cytoplasm and induce transcription factor of target proteins. A larger size of the image can be found in the resource list.