@article{0310aa03f70043778fd499ef95eb2799,
title = "CB1 cannabinoid receptor-phosphorylated fourth intracellular loop structure-function relationships",
abstract = "A peptide comprising the juxtamembrane C-terminal intracellular loop 4 (IL4) of the CB1 cannabinoid receptor possesses three serine residues (Ser402, Ser411, and Ser415). We report the effect of Ser phosphorylation on the CB1 IL4 peptide conformation and cellular signaling functions using nuclear magnetic resonance spectroscopy, circular dichroism (CD), G protein activation, and cyclic adenosine monophosphate (cAMP) production. Phosphorylation at Ser residues induced helical structure in different environments. Helical content varies in the order of IL4p-Ser411 > IL4pSer415 > IL4 > IL4pSer402. The efficacy of phosphorylated IL4 peptides in activating Go and Gi3 ([35S]GTPγS binding) and inhibiting cAMP accumulation in N18TG2 cells was correlated with helicity changes. Bradykinin treatment, which activates protein kinase C (PKC), augmented CB1-mediated inhibition of cAMP accumulation, and this was reversed by a PKC inhibitor. We conclude that phosphorylation-dependent alterations of helicity of CB1 IL4 peptides can augment G protein signaling.",
keywords = "G protein-coupled receptors (GPCR), bradykinin, endocannabinoid, pepducin, phosphorylation, protein kinase C (PKC)",
author = "Khalil Eldeeb and Ganjiwale, {Anjali D.} and Chandrashekaran, {Indu R.} and Padgett, {Lea W.} and Burgess, {Jason P.} and Howlett, {Allyn C.} and Cowsik, {Sudha M.}",
note = "Funding Information: information Jawaharlal Nehru University, Grant/Award Number: UPE II grant and DST Purse grant of JNU, Delhi,UGC; National Institute of General Medical Sciences, Grant/Award Number: K12-GM102773; National Institute on Drug Abuse, Grant/Award Number: R01-DA03690 and U24-DA12385; JNU, Delhi, UGC faculty recharge scheme; NIH, Grant/Award Numbers: K12-GM102773, U24-DA12385, R01-DA03690The authors thank Pratishtha Singh and Sandra Kabler for help with figure preparation. We also acknowledge the NMR Research Centre, Indian Institute of Science, and RTI, International for providing the facilities to record NMR experiments. SMC acknowledge support from DST Purse grant JNU and UPE II grant Govt. of India. ADG acknowledges DST Purse grant, Bangalore University and UGC Faculty Recharge Program, Govt. of India. Funding Information: The authors thank Pratishtha Singh and Sandra Kabler for help with figure preparation. We also acknowledge the NMR Research Centre, Indian Institute of Science, and RTI, International for providing the facilities to record NMR experiments. SMC acknowledge support from DST Purse grant JNU and UPE II grant Govt. of India. ADG acknowledges DST Purse grant, Bangalore University and UGC Faculty Recharge Program, Govt. of India. Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",
year = "2019",
month = jul,
doi = "10.1002/pep2.24104",
language = "English",
volume = "111",
journal = "Peptide Science",
issn = "2475-8817",
number = "4",
}