The roles of PDZ-containing proteins in PLC-beta-mediated signaling.
Mammalian phospholipase C-beta isozymes are activated by a heterotrimeric GTP-binding protein linked to various cell surface receptors. Recent reports suggest that PDZ domain proteins play a significant role of PDZ-containing proteins in the regulation of mammalian PLC-beta isozymes. PDZ-containing proteins mediate the clustering of receptors and signaling molecules and thereby regulate agonist-induced signal transduction in polarized cells such as neuronal and epithelial cells. NORPA, a Drosophila PLC-beta, is known to be a component of a signaling complex that includes TRP and rhodopsin through interaction with INAD, a PDZ-containing protein. Mammalian PLC-beta1 and -beta2 isoforms interact with a PDZ-containing protein NHERF which is coupled to Trp4, a Ca(2+) channel. In addition, PLC-beta3 specifically interacts with E3KARP, another protein closely related to NHERF, through its C-terminal PDZ-binding motif. E3KARP up-regulates the PLC-beta3 activation coupled to muscarinic receptor. In this review, the role of signaling complexes mediated by PDZ-containing proteins in the regulation of PLC-beta isoforms will be discussed.
Suh
P G
PG
Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea. pgs@postech.ac.kr
Hwang
J I
JI
Ryu
S H
SH
Donowitz
M
M
Kim
J H
JH
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000502:physiology; D004330:Drosophila / Q000502:physiology; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D054799:Phospholipase C beta; D010750:Phosphoproteins / Q000502:physiology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers; D050052:TRPC Cation Channels; D010738:Type C Phospholipases / Q000737:chemistry / Q000502:physiology*; D014785:Vision, Ocular
D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; C091568:inaD protein, Drosophila; C093376:sodium-hydrogen exchanger regulatory factor; D010738:Type C Phospholipases; D054799:Phospholipase C beta