Biochemical and cell biological mechanisms of cholecystokinin receptor regulation

Laurence J Miller, Maoqing Dong, Kaleeckal G. Harikumar, Cayle S. Lisenbee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Regulation of the cholecystokinin receptor is accomplished by biochemical and cell biological mechanisms. The major mechanism for biochemical regulation involves phosphorylation of serine and threonine residues within the receptor's intracellular third loop and carboxyl-terminal tail. This form of rapid desensitization is achieved by protein kinase C, a kinase activated in the normal signaling cascade of this Gq-coupled receptor, and/or a member of the G protein-coupled receptor kinase family that recognizes the active conformation of the receptor. Conversely, a type 2A serine protein phosphatase has been shown to selectively act on this receptor in an agonist-regulated manner, resulting in receptor dephosphorylation and resensitization. Cell biological mechanisms for desensitization involve the net removal of receptors from exposure to circulating hormone via insulation within a specialized plasma membrane domain or internalization into the cell within endocytic compartments. Internalization has been shown to occur by both clathrin-dependent and clathrin-independent mechanisms, the latter believed to represent potocytosis in caveolae, that lead to recycling of receptors to the plasma membrane for resensitization or shuttling of receptors to lysosomes for degratory down-regulation. Interestingly, receptor phosphorylation has been shown to affect intracellular domain accessibility and receptor trafficking, although the specific proteins regulating this have not yet been identified. The cholecystokinin receptor can exist in the plasma membrane as oligomeric superstructures, namely as homomers with themselves or as heteromers with closely related class I G protein-coupled receptors. Agonist occupation results in oligomer dissociation, but the functional significance of this observation has yet to be defined.

Original languageEnglish (US)
Pages (from-to)1166-1172
Number of pages7
JournalCurrent Topics in Medicinal Chemistry
Volume7
Issue number12
DOIs
StatePublished - Jun 2007

Fingerprint

Cholecystokinin Receptors
Cell membranes
Clathrin
Phosphorylation
Cell Membrane
Serine
G-Protein-Coupled Receptor Kinases
Caveolae
Protein Phosphatase 2
Phosphoprotein Phosphatases
Threonine
G-Protein-Coupled Receptors
Lysosomes
Occupations
Oligomers
Protein Kinase C
Conformations
Recycling
Insulation
Phosphotransferases

Keywords

  • CCK-binding domain
  • G protein-coupled receptor
  • Oligomerization
  • S260 phosphorylation
  • YFP fluorescence

ASJC Scopus subject areas

  • Medicine(all)
  • Chemistry(all)

Cite this

Biochemical and cell biological mechanisms of cholecystokinin receptor regulation. / Miller, Laurence J; Dong, Maoqing; Harikumar, Kaleeckal G.; Lisenbee, Cayle S.

In: Current Topics in Medicinal Chemistry, Vol. 7, No. 12, 06.2007, p. 1166-1172.

Research output: Contribution to journalArticle

Miller, Laurence J ; Dong, Maoqing ; Harikumar, Kaleeckal G. ; Lisenbee, Cayle S. / Biochemical and cell biological mechanisms of cholecystokinin receptor regulation. In: Current Topics in Medicinal Chemistry. 2007 ; Vol. 7, No. 12. pp. 1166-1172.
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