Table 1. AR-associated kinases.
Kinases that are transcriptionally (top part) or translationally (middle part) regulated by AR and kinases that interact with AR (bottom part). Up/down; kinase expression induced/repressed by AR. Inhibitors; commercially available kinase inhibitors, information obtained from genecards.org. CaP phosphoproteome; site of kinase phosphorylation in CRPC samples obtained from Faltermeier et al., 2016 and Drake et al., 2016. NA, not applicable.
| Gene Symbol | AR-dependence | Type | Family | Inhibitor | CaP phosphoproteome |
|---|---|---|---|---|---|
| AR regulation: | transcriptional | ||||
| BMPR1A | up | Ser/Thr | TKL | DMH-1 | NA |
| BMPR1B | up | Ser/Thr | TKL | LDN-212854 | NA |
| CAMKK2 | up | Ser/Thr | CAMK | A 484954, NH125 | pS495, pS511c |
| CDK8 | down | Ser/Thr | CMGC | Senexin A | NA |
| CDKL5 | down | Ser/Thr | CMGC | None | NA |
| CLK2 | down | Ser/Thr | CMGC | TG003 | NA |
| DDR1 | down | Tyr | TK | DDR1-IN-1, nilotinib | Y520, Y792, Y796 d |
| EPHA3 | up | Tyr | TK | KB004 | Y596 d |
| ERBB2a | down | Tyr | TK | >90 inhibitors | pS1054, pS1078, pS1083 c |
| MAK1a | up | Ser/Thr | CMGC | None | NA |
| MAP2K4 | up | Ser/Thr | STE | MEK inhibitors | pS257 c |
| MAP4K1 | down | Ser/Thr | STE | None | NA |
| MAPK6b | up | Ser/Thr | CMGC | None | pS386, pT389 e |
| MAPK8 | down | Ser/Thr | CMGC | None | pT183 d |
| MAPKAPK3 | down | Ser/Thr | CAMK | None | NA |
| MERTK | up | Tyr | TK | None | NA |
| MYLK | down | Ser/Thr | CAMK | ML 9 Hydrochloride | pS911, pS1768 c |
| PAK2 | down | Ser/Thr | STE | FRAX597 | pS2, pS141 c |
| PRKAA1 | up | Ser/Thr | CAMK | None | pS496 c |
| PRKCA | up | Ser/Thr | AGC | None | pT638, pS657 f |
| PRKD1a | down | Ser/Thr | CAMK | CID 2011756 | pS473 e |
| ROR1 | up | Tyr | TK | None | NA |
| RPS6KA1a | down | Ser/Thr | AGC | BRD 7389 | pS232 e |
| RPS6KA3a | up | Ser/Thr | AGC | AT9283 | pS221 e |
| SGK1a | up | Ser/Thr | AGC | None | NA |
| SNRK | down | Ser/Thr | CAMK | None | NA |
| STK17B | up | Ser/Thr | CAMK | None | NA |
| STK39 | up | Ser/Thr | STE | None | pS385, pS315, pT354 c |
| AR regulation: | translational | ||||
| HIPK3a | NA | Ser/Thr | CMGC | None | NA |
| MAPK6b | NA | Ser/Thr | CMGC | None | pS386, pT389 e |
| MAPKAPK2 | NA | Ser/Thr | CAMK | PF-3644022 | NA |
| PINK1 | NA | Ser/Thr | Other | None | NA |
| TRIM24a | NA | Ser/Thr | Atypical | None | pS1028 c |
| AR regulation: | interactor | ||||
| AKT1 | NA | Ser/Thr | AGC | Nelfinavir, Everolimus, PHT 427 | pT34 c |
| CDK11B | NA | Ser/Thr | CMGC | None | pS265, pS271, pS422 c |
| CDK6 | NA | Ser/Thr | CMGC | LEE011 - CDK4/6 | NA |
| CDK7 | NA | Ser/Thr | CMGC | Alvocidib, seliciclib, BS-181 | pS164 g |
| CDK9 | NA | Ser/Thr | CMGC | Alvocidib, seliciclib, Dinaciclib, AZD 5438 | NA |
| DAPK3 | NA | Ser/Thr | CAMK | None | NA |
| DYRK1A | NA | Ser/Thr | CMGC | Harmine, INDY, ProINDY | pY321 f |
| EGFR | NA | Tyr | TK | >200 inhibitors | pS1039, pS1042 c |
| ERBB2a | NA | Tyr | TK | >90 inhibitors | pS1054, pS1078, pS1083 c |
| GAK | NA | Ser/Thr | Other | None | pS16, pS73, pS826, pS829, pS1185 c |
| GSK3B | NA | Ser/Thr | CMGC | SB 216763, AZD1080 | pY216 d |
| HIPK3a | NA | Ser/Thr | CMGC | None | NA |
| LATS2 | NA | Ser/Thr | AGC | None | NA |
| MAK1a | NA | Ser/Thr | CMGC | None | NA |
| MAPK1 | NA | Ser/Thr | CMGC | FR 180204 | Y187 d |
| MAPK15 | NA | Ser/Thr | CMGC | None | NA |
| NLK | NA | Ser/Thr | CMGC | None | NA |
| PAK6 | NA | Ser/Thr | STE | None | pS560 d |
| PKN1 | NA | Ser/Thr | AGC | lestaurtinib, tofaticinib | pS69, pS916 d |
| PRKD1a | NA | Ser/Thr | CAMK | CID 2011756 | pS473 e |
| PRKDC | NA | Ser/Thr | Atypical | AZD7648, | pT2609, pS2612, pS3205 d |
| RNASEL | NA | Ser/Thr | Other | None | NA |
| RPS6KA1a | NA | Ser/Thr | AGC | BRD 7389 | pS232 e |
| RPS6KA3a | NA | Ser/Thr | AGC | AT9283 | pS221 e |
| SGK1a | NA | Ser/Thr | AGC | None | NA |
| SRC | NA | Tyr | TK | Herbimycin A, MNS, Dasatinib | pS104 e |
| TAF1 | NA | Ser/Thr | Atypical | None | pS1152, pS1155, pS1669, pS1672 e |
| TNK2 | NA | Tyr | TK | AIM-100, Dasatinib | pY827 e |
| TRIM24a | NA | Ser/Thr | Atypical | None | pS1028 c |
, entry occurs in top and bottom part of table;
, entry occurs in top and middle part of table;
phosphorylation site is significantly enriched in CaP but functional consequence of phosphorylation is unknown;
phosphorylation site is significantly enriched in CaP and associated with kinase activation;
phosphorylation site is found but not significantly enriched in CaP and functional consequence of phosphorylation is unknown;
phosphorylation site not significantly enriched in CaP but activates the kinase;
phosphorylation site is significantly enriched in CaP and represses kinase activity. Ser/thr, serine/threonine kinase; Tyr, tyrosine kinase; TKL, Tyrosine Kinase-Like; CAMK, Calcium/Calmodulin dependent-kinase; TK, Tyrosine Kinase; CMGC, members of cyclin-dependent kinase, mitogen-activated protein kinase, glycogen synthase kinase and CDC-like kinase; AGC, members of PKA, PKG, and PKC; STE, “Sterile” serine/threonine kinases;