Table 2.
G protein signalling properties of full‐length chemokines and peptides derived from their N‐terminal regions towards CXCR4 and CXCR3
| Name | Sequence | cAMP | Calcium | ||||||
|---|---|---|---|---|---|---|---|---|---|
| CXCR4 | CXCR3 | CXCR4 | CXCR3 | ||||||
| pEC50 ± SEM | Max (%) | pEC50 ± SEM | Max (%) | pEC50 (pIC50) ± SEM | Max (%) | pEC50 (pIC50) ± SEM | Max (%) | ||
| CXCL12 | – | 8.97 ± 0.09 | 100 | <6.00 | 2 | 8.84 ± 0.05 | 100 | <6.00 | 0 |
| CXCL121–17 | KPVSLSYRCPCRFFESH | 5.67 ± 0.06 | 103 | <4.00 | 1 | 5.58 ± 0.04 | 44 | <4.00 | 0 |
| CXCL121–9 | KPVSLSYRS | 5.11 ± 0.09* | 101 | ND | <4.00 | 16 | ND | ||
| (CXCL121–9)2 | (KPVSLSYRC)2 | 6.07 ± 0.06* | 105 | ND | ND | ND | |||
| CXCL121–17D | KPVSLSYRCPCRFFESH | <4.00 | 6 | ND | (<4.00) | 0 | ND | ||
| CXCL122–17 | ‐PVSLSYRCPCRFFESH | <4.00 | 1 | ND | (4.50 ± 0.12) | 0 | ND | ||
| CXCL121–17/P2G | KGVSLSYRCPCRFFESH | <4.00 | 1 | ND | (4.45 ± 0.06) | 0 | ND | ||
| vCCL2 | – | <6 | 0 | <6.00 | (7.67 ± 0.08) | 0 | <6.00 | 0 | |
| vCCL21–21 | LGASWHRPDKCCLGYQKRPLP | <4.00 | 0 | <4.00 | 0 | (5.15 ± 0.05) | 0 | <4.00 | 0 |
| vCCL21–11 | LGASWHRPDKS | <4.00 | 0 | ND | (<4) | 0 | ND | ||
| (vCCL21–11)2 | (LGASWHRPDKC)2 | <4.00 | 0 | ND | ND | ND | |||
| vCCL21–21D | LGASWHRPDKCCLGYQKRPLP | <4.00 | 0 | ND | (5.16 ± 0.04) | 0 | ND | ||
| CXCL11 | – | <6.00 | 1 | 8.46 ± 0.06 | 100 | <6.00 | 0 | 7.72 ± 0.13 | 100 |
| CXCL111–17 | FPMFKRGRCLCIGPGVK | <4.52a | 0 | <4.52a | 4 | <4.30b | 0 | 4.32 ± 0.04b | 78 |
| CXCL111–9 | FPMFKRGRS | ND | 0 | 4.45 ± 0.08 | 89 | ND | 4.79 ± 0.05* | 37 | |
| (CXCL111–9)2 | (FPMFKRGRC)2 | ND | 0 | 5.35 ± 0.07* | 95 | ND | ND | ||
| CXCL111–17D | FPMFKRGRCLCIGPGVK | ND | 0 | <4.52a | 4 | ND | (5.13 ± 0.06)b | 0 | |
| CXCL112–17 | ‐PMFKRGRCLCIGPGVK | ND | 0 | <4.52a | 2 | ND | (5.32 ± 0.15)b | 0 | |
| CXCL111–17/P2G | FGMFKRGRCLCIGPGVK | ND | 0 | <4.52a | 0 | ND | (5.73 ± 0.19)b | 0 | |
| CXCL10 | – | <6.00 | 0 | 8.36 ± 0.12 | 97 | <6.00 | 0 | 7.76 ± 0.19 | 100 |
| CXCL101–17 | VPLSRTVRCTCISISNQ | <4.00 | 0 | <4.52a | 0 | <4.30b | 0 | 4.58 ± 0.03 | 112 |
| CXCL9 | – | <6.00 | 0 | 6.47 ± 0.10 | 85 | <6.00 | 0 | 6.73 ± 0.15 | 100 |
| CXCL91–17 | TPVVRKGRCSCISTNQG | <4.00 | 0 | <4.00 | 0 | <4.00 | 0 | <4.00 | 0 |
cAMP modulation measurements were performed in U87 cells using GloSensor technology (n = 5). Peptides 1‐17 (for CXCL12 and CXCL11) and 1‐21 (for vCCL2) were considered as the standard, reference peptides and monomeric mutant peptides were compared with these. Where dimeric peptides were assessed, these were compared with their corresponding monomeric peptides.
P < 0.05, significantly different from standard peptides or from monomeric peptides; ns, not significant, P > 0.05.
Highest concentration tested 30 μM. Intracellular calcium release was evaluated in U87 cells using a calcium‐responsive fluorescent probe and an FLIPR system (n = 5).
Highest concentration tested 50 μM. ND: not determined. (Data antagonist mode).