Table 1.
The peptides, derivatives of signal proteins, and their biological activity.
| Signal protein | Sequence | Activity | References | |
|---|---|---|---|---|
| α 2-AR (C-ICL3) | RWRGRQNREKRFTC361-373 and its dimeric constrain with N-ICL3-peptide RIYQIAKRRTR233-243 | Both selectively stimulate Gi/o proteins and inhibit α 2-AR agonist-stimulated GTPase activity | [30–32] | |
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| β 2-AR (C-ICL3) | RRSSKFCLKEKKALK259-273 | Selectively stimulates Gs proteins and decreases regulatory effects of β 2-AR agonists | [33–35] | |
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| D1-DR (C-ICL3, I), 5-HT6R (C-ICL3, II) | FKMSFKRETKVLKTLSV260-276 (I); KHSRKALKASL258-268K (II) | Stimulate Gs proteins and AC activity, decrease the stimulating effects of D1-DR (peptide I) and 5-HT6R (II) on AC system | [38, 39] | |
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| D2-DR (N-ICL3, I), 5-HT1AR (N-ICL3, II); 5-HT1BR (C-ICL3, III); 5-HT1DR (N-ICL3, IV; C-ICL3, V); m4-MChR (C-ICL3, VI) | VYIKIYIVLRRRRKRVNTK206-224 (I); LYGRIFRAARFRIRKTVK214-231 (II); ARERKATKTL307-316 (III); LYGRIYVAARSRI213-225 (IV); RKRISAARERKATK285-298 (V); RNQVRKKRQMAARERKVTR382-400 (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] | |
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| m3-MChR (C-ICL3) | LVKEKKAAQTLSAILL483-497 | Selectively activates Gq and influences m3-MChR-mediated signaling | [43] | |
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| δ-opioid receptor (ICL3) | MGRLRSVRLLSGSKEKDRSLRRITR237-261 | Blocks δ-agonist-induced PLC activation, Ca2+ release and cAMP signaling | [45] | |
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| Luteinizing hormone receptor; FSH receptor (C-ICL3, II); relaxin receptor RXFP1 (C-ICL3, III); parathyroid hormone receptor (C-ICL3, IV) | FAVQNPELMATNKDTKIAKK551-570 (I), HIYLTVRNPNIVSSSSDTRIAKR533-555 (II), and EIRNQVKKE(Nle)ILAKR615-629 (III) and their short analogs; EYRKLLK402-408 (IV) |
Activate preferably Gs proteins and stimulate the basal AC activity, inhibit agonist-induced signaling via their cognate receptors | [46–52] | |
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| GLP1R (ICL1 and ICL3) | FRHLHCTR169-176; IVIAKLKANLMCKTDIKCRLAK330-351 | Activate preferably Gs and Gi proteins, inhibit hormone- stimulated AC activity | [53] | |
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| V2-vasopressin receptor (ICL3) | Cyclo-QVLIFREIHASLVPGPSERAG-RRRRGRRTGSPSEGAHVSAAMAKT-VRMT225-273 | Decreases the affinity of agonist for the receptor and inhibits vasopressin-stimulated AC activity | [55] | |
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| 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] | |
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| 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] | |
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| Prostacyclin receptor (ICL1) | SARRPARPSAFAV39-51 | Selectively stimulates Gs proteins and the basal activity of AC | [65, 66] | |
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| 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] | |
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| Insulin receptor (C-terminal region) | N-stearyl-SSHCQREEAGGRDGG1293-1307 | Enhances insulin-stimulated autophosphorylation; increases insulin-stimulated PI3K and MAPK activities | [68] | |
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| EGF receptor (N-terminal region of the juxtamembrane domain) | RRREIVRKRTLRR646-658 | Activates Gs proteins, influences activity of Gi proteins | [69] | |
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| NPR-C (cytoplasmic domain) | KKYRITIERRNH461-472; RRNHQEESNIGK469-480; RRNHQEESNIGKHRELR469-485; HRELREDSIRSH481-492 and their analogs |
Inhibit the basal, forskolin- and hormone-stimulated AC activity; selectively increase GTP binding activity of Gi1 and Gi2 proteins; stimulate PLCβ3 activity; inhibit hormone-stimulated DNA synthesis in vascular smooth muscle cells; induce smooth muscle contraction | [70–72] | |
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| 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] | |
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| Gα t | IKENLKDCGLF340-350 | Stabilizes the active state of opsin and meta-II-rhodopsin and meta-Ib-rhodopsin; | [73–76] | |
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| Gα s | RVFNDARDIIQRMHLRQYELL374-394 and its short analogs | Inhibit transduction of hormonal signal via Gs-coupled receptors | [77] | |
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| Gα s (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] | |
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| Gα s (α3-β5 region) | EALNLFKSIWNNRWL-RTIS268-286 | Inhibits the basal and forskolin-stimulated activities of AC2 and AC6; significantly decreases the Gα s-stimulated enzyme activity | [78] | |
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| 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 μM | [80] | |
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| AC2 (C2 domain) | YTESDVNKEGLECLRLLNEIIADFD-DLL899-926 (α2, I); SKPKFSGVEKIKTIGSTYMAAT927-948 (β2-β3, II); DAINKHSFNDFKLRVGINHGPVIA-GVIGAQK984-1015 (α3-β4, III) |
All peptides inhibit Gα s- and forskolin-stimulated activities of AC2 and AC6; peptides I and III inhibit the basal AC activity; peptide I decreases Mn2+-stimulated activity | [81] | |
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| AC6 (C1 domain) | AAENHCLRIKILGDCYYC427-444 (α2-β2-β3, I); IHSGRVHCGVLGLRKWQFDVWSN-DV487-511 (β4-β5-α4, II) | Both peptides inhibit Gα s- and forskolin-stimulated AC activities; peptide II inhibits the basal activity of both AC2 and AC6 | [81] | |
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| PLCβ1b | N-Myristoyl-TPPNPQALKW1164-1173 (I); GEGSSSVLSESCHEDPSVPPNFTPP-NPQALKW1142-1173 (II) |
Both peptides dissociate the enzyme from membrane and inhibit PLC stimulation by hormones; peptide II prevents cardiomyocytes hypertrophy | [82, 83] | |
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| PLCβ3 | QEENTQL1161-1167 | Significantly inhibits intracellular calcium response to selective agonists of mGluR | [84] | |
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| PLCγ | GLYRKAMRLRYPV724-736, and its N-myristoylated analogs | Specifically inhibit PLC activity and PLC-dependent cellular processes | [85] | |
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| PLCδ1 (IQ-peptide) | VRSQVQHKPKEDKLKLVPELS473-493 | Inhibits PLC activity; binds CaM in Ca2+-independent manner | [86] | |
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| PLCδ1 | N-Myristoyl-TIPWNSLKQGYRHVHLL747-763 | Inhibits FSH-induced Ca2+ influx | [87] | |
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| 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] | |
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| PKCζ (pseudosubstrate region) | N-Myristoyl-SIYRRGARRWRKL114-126 | Inhibits PKCζ activity; stimulates Akt, ERK1/2, p38 MAPK and eNOS activity | [89] | |
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| PKCη (pseudosubstrate region) | N-Myristoyl-RKRQRAMRRRVHQING156-171 | Inhibits PKCη activity; stimulates eNOS phosphorylation | [89] | |