Signal protein Sequence Activity References
-AR (C-ICL3)RWRGRQNREKRFTC361-373 and its dimeric constrain with N-ICL3-peptide RIYQIAKRRTR233-243 Both selectively stimulate Gi/o proteins and inhibit
-AR agonist-stimulated GTPase activity [30 –32 ]
-AR (C-ICL3)RRSSKFCLKEKKALK259-273 Selectively stimulates Gs proteins and decreases regulatory effects of β 2 -AR agonists [33 –35 ] D1 -DR (C-ICL3, I), 5-HT6 R (C-ICL3, II) FKMSFKRETKVLKTLSV260-276 (I); KHSRKALKASL258-268 K (II) Stimulate Gs proteins and AC activity, decrease the stimulating effects of D1 -DR (peptide I) and 5-HT6 R (II) on AC system [38 , 39 ] D2 -DR (N-ICL3, I), 5-HT1A R (N-ICL3, II); 5-HT1B R (C-ICL3, III); 5-HT1D R (N-ICL3, IV; C-ICL3, V); m4 -MChR (C-ICL3, VI) VYIKIYIVLRRRRKRVNTK206-224 (I); LYGRIFRAARFRIRKTVK214-231 (II); ARERKATKTL307-316 (III);213-225 (IV); 285-298 (V); 382-400 (VI) Selectively activate Gi/o proteins and inhibit forskolin-stimulated AC activity in the absence of hormone; inhibit signaling via their cognate Gi/o -coupled receptors [30 , 32 , 39 –42 ] m3 -MChR (C-ICL3) LVKEKKAAQTLSAILL483-497 Selectively activates Gq and influences m3 -MChR-mediated signaling [43 ] δ -opioid receptor (ICL3)MGRLRSVRLLSGSKEKDRSLRRITR237-261 Blocks δ -agonist-induced PLC activation, Ca2+ release and cAMP signaling [45 ] Luteinizing hormone receptor; FSH receptor (C-ICL3, II); relaxin receptor RXFP1 (C-ICL3, III); parathyroid hormone receptor (C-ICL3, IV) FAVQNPELMATNKDTKIAKK551-570 (I), 533-555 (II), 615-629 (III) 402-408 (IV) Activate preferably Gs proteins and stimulate the basal AC activity, inhibit agonist-induced signaling via their cognate receptors [46 –52 ] GLP1R (ICL1 and ICL3) FRHLHCTR169-176 ; IVIAKLKANLMCKTDIKCRLAK330-351 Activate preferably Gs and Gi proteins, inhibit hormone- stimulated AC activity [53 ] V2 -vasopressin receptor (ICL3) Cyclo-QVLIFREIHASLVPGPSERAG-RRRRGRRTGSPSEGAHVSAAMAKT-VRMT225-273 Decreases the affinity of agonist for the receptor and inhibits vasopressin-stimulated AC activity [55 ] CB1 -cannabinoid receptor (N-ICL3, I; C-ICL3, II, and N-CTD, III) KAHSHAVRMIQRGTQKS301-317 (I); QVTRPDQARMDIRLAK329-344 (II); RSKDLRHAFRSMFPSCE401-417 (III) Selectively stimulate different isoforms of the α -subunits of Gi proteins and significantly inhibit AC activity [56 –58 ] Angiotensin II receptor of the type 1 (ICL2, I; N-ICL3, II; C-ICL3, III, N-CTD, IV) DRYLAIVHPMKSR125-137 (I); TLIWKALKKAYEIQKN216-231 (II); KNKPRNDDIFRI230-241 (III); FLGKKFKKYFLQL304-316 (IV) Inhibit angiotensin-induced activation of G proteins and the effector enzymes; peptide II selectively activates Gi/o proteins, peptide III Gq/11 proteins [59 –62 ] FPR1 (ICL2, I; N-CTD, II) CVLHPVWTQNHR126-137 (I); FRERLIHALPASLER308-322 (II) Activate in a PTX-dependent manner Gi proteins; peptide II inhibits high affinity agonist binding to the receptor and its coupling to Gi protein [63 , 64 ] Prostacyclin receptor (ICL1) SARRPARPSAFAV39-51 Selectively stimulates Gs proteins and the basal activity of AC [65 , 66 ] Insulin receptor (tyrosine kinase region) N-stearyl-TRDIYETDYYRK1142-1153 Increases insulin- and vanadate-stimulated phosphorylation of IR; significantly enhances insulin-induced stimulation of PI3K and MAPK activities [67 ] Insulin receptor (C-terminal region) N-stearyl-SSHCQREEAGGRDGG1293-1307 Enhances insulin-stimulated autophosphorylation; increases insulin-stimulated PI3K and MAPK activities [68 ] EGF receptor (N-terminal region of the juxtamembrane domain) RRREIVRKRTLRR646-658 Activates Gs proteins, influences activity of Gi proteins [69 ] NPR-C (cytoplasmic domain) KKYRITIERRNH461-472 ; 469-480 ; 469-485 ; 481-492 and their analogs Inhibit the basal, forskolin- and hormone-stimulated AC activity; selectively increase GTP binding activity of Gi1 and Gi2 proteins; stimulate PLCβ 3 activity; inhibit hormone-stimulated DNA synthesis in vascular smooth muscle cells; induce smooth muscle contraction [70 –72 ] NPR-C (extreme C-terminal region of the cytoplasmic domain) GKHRELREDSIRSHFSVA479-496 Inhibits ANP(4–23)-induced Gi protein activation and cellular responses acting as a competitive inhibitor of ANP(4–23)-mediated signaling [71 ]
IKENLKDCGLF340-350 Stabilizes the active state of opsin and meta-II-rhodopsin and meta-Ib-rhodopsin; [73 –76 ]
RVFNDARDIIQRMHLRQYELL374-394 and its short analogs Inhibit transduction of hormonal signal via Gs -coupled receptors [77 ]
(Switch I and II regions, resp.)RCRVLTSGIFETKFQVDK199-216 ; FDVGGQRDERRKWIQ-CFNDVTAIIFV222-247 Increase the basal and forskolin-stimulated AC2 and AC6 activities; inhibit Gα s -stimulated activity of both AC isoforms; behave as partial agonist [78 ]
(α 3-β 5 region)EALNLFKSIWNNRWL-RTIS268-286 Inhibits the basal and forskolin-stimulated activities of AC2 and AC6; significantly decreases the Gα s -stimulated enzyme activity [78 ] AC1 (C1b subdomain) IKPAKRMKFKTVCYLLVQLMHCRKMF-KA495-522 (pAC28, C1b ) Binds CaM with high affinity in a Ca2+ -independent manner; inhibits CaM-stimulated AC activity with IC50 equal to 500 nM [79 , 80 ] AC1 (C2a subdomain) TEEVHRLLRRGS-YRFVCRGKV1024-1044 (pVLG, C2a ) Binds CaM with low affinity in a Ca2+ -dependent manner; inhibits CaM-stimulated AC activity with IC50 is 10
M [80 ] AC2 (C2 domain) YTESDVNKEGLECLRLLNEIIADFD-DLL899-926 (α 2, I); 927-948 (β 2-β 3, II); 984-1015 (α 3-β 4, III) All peptides inhibit G
- and forskolin-stimulated activities of AC2 and AC6; peptides I and III inhibit the basal AC activity; peptide I decreases Mn2+ -stimulated activity [81 ] AC6 (C1 domain) AAENHCLRIKILGDCYYC427-444 (α 2-β 2-β 3, I); IHSGRVHCGVLGLRKWQFDVWSN-DV487-511 (β 4-β 5-α 4, II) Both peptides inhibit G
- and forskolin-stimulated AC activities; peptide II inhibits the basal activity of both AC2 and AC6 [81 ] PLCβ 1b N-Myristoyl-TPPNPQALKW1164-1173 (I); 1142-1173 (II) Both peptides dissociate the enzyme from membrane and inhibit PLC stimulation by hormones; peptide II prevents cardiomyocytes hypertrophy [82 , 83 ] PLCβ 3 QEENTQL1161-1167 Significantly inhibits intracellular calcium response to selective agonists of mGluR [84 ] PLCγ GLYRKAMRLRYPV724-736 , and its N-myristoylated analogs Specifically inhibit PLC activity and PLC-dependent cellular processes [85 ] PLCδ 1 (IQ-peptide) VRSQVQHKPKEDKLKLVPELS473-493 Inhibits PLC activity; binds CaM in Ca2+ -independent manner [86 ] PLCδ 1 N-Myristoyl-TIPWNSLKQGYRHVHLL747-763 Inhibits FSH-induced Ca2+ influx [87 ] Regulatory p85-subunit of PI3K (C-terminal region of N-terminal SH2 domain) WNVGSSNRNKAENLLRGKR11-29 Exhibits binding specificity and affinity for PI 3,4,5-P3 and inhibits PI 3,4,5-P3 -binding to the p85 subunit [88 ] PKCζ (pseudosubstrate region) N-Myristoyl-SIYRRGARRWRKL114-126 Inhibits PKCζ activity; stimulates Akt, ERK1/2, p38 MAPK and eNOS activity [89 ] PKCη (pseudosubstrate region) N-Myristoyl-RKRQRAMRRRVHQING156-171 Inhibits PKCη activity; stimulates eNOS phosphorylation [89 ]
