TABLE 1.
Protein partners very likely or shown to interact directly with Pyk2.
| Partner | Partner binding region | Binding site in Pyk2 | Comments | References |
| ArgBP2 | SH3A | PR2 and/or PR3 | PC12, HEK293T; co-IP, GST pull-down; complex with Pyk2, Cbl | Haglund et al. (2004) |
| ASAP1 / DEF-1 / PIP2-dependent ARF1 GAP | SH3 | PR2 and/or PR3 | Rat brain, HEK293, PC12; Pyk2 P717A or P859A reduces ASAP1 phosphorylation | Kruljac-Letunic et al. (2003) |
| ASAP2 / PAG3 / PAP | SH3? | Andreev et al. (1999) | ||
| BCAR1 / p130cas | SH3 | PR2 and/or PR3 | Astier et al. (1997); Manie et al. (1997); Ohba et al. (1998); Anfosso et al. (2001); Takahashi et al. (2003) | |
| Related to p130Cas: embryonal Fyn-associated substrate (EFS)/ SIN | SH3 | 670–792 | Interacts more with FAK than Pyk2 | Ohba et al. (1998) |
| Related to p130Cas: enhancer of filamentation 1 (hEF1 / NEDD9 / CasL) | SH3 | PR2 and/or PR3 | Similar to p130-Cas | Manie et al. (1997) |
| Calmodulin | With Ca2+ | FERM, kinase, KFL | Multiple, see text | Kohno et al. (2008); Xie et al. (2008); Vomaske et al. (2010) |
| Disks large homolog 3 (DLG3) / Synapse-associated protein 102 (SAP102) | SH3 | PR2 and/or PR3 | Seabold et al. (2003) | |
| Disks large homolog 4 (DLG4) / PSD-95 | SH3 | PR2 and/or PR3 | Requirement of the proline-rich region of Pyk2 for binding to PSD-95 and SAP102 | Seabold et al. (2003) |
| FGFR-2, -3c | C-ter | Kinase domain? | Meyer et al. (2004) | |
| Gelsolin | C-ter | PR3 | HEK293, co-IP formation of osteoclastic actin rings | Wang et al. (2003) |
| Graf1C (RhoA GTPase-activating protein) | SH3 | PR3 > PR2 | Pyk2 inhibits Graf1c (requires kinase activity) | Lee et al. (2019) |
| Grb2 | SH2 | pTyr881 | Grb2/Ras/Raf/MEK activates ERK1/2 after short treatment of GT1-7 cells with GnRH | Li et al. (1996); Ganju et al. (1997); Blaukat et al. (1999); Bruzzaniti et al. (2009); Okitsu-Sakurayama et al. (2018) |
| Grm1, metabotropic glutamate receptor 1, mGluR1 | 2nd intracellular loop, C-ter tail | Pyk2 displaces Gαq/11 from the receptor and activates ERK | Nicodemo et al. (2010) | |
| Grm5, metabotropic glutamate receptor 5, mGluR5 | 2nd intracellular loop, C-ter tail | Similar effects as Grm1? | Nicodemo et al. (2010) | |
| Integrin beta-3 / CD61 / GP3a | C-ter 17 aa | N-terminal | Pyk2 downstream of β3; in vitro binding | Pfaff and Jurdic (2001) |
| Megakaryocyte-associated tyrosine-protein kinase / CsK homologous kinase (CHK) / MATK | SH2 | pY402 | CHK inhibits Pyk2 phosphorylation; co-IP | McShan et al. (2002) |
| Membrane-associated phosphatidylinositol transfer protein 1, 2, 3 / PITPnm 1, 2, 3 / NIR-2, -3, -1/RdgB-homologs | C-terminal | FERM | Yeast two-hybrid assay; binding, co-IP, Pyk2 substrates | Lev et al. (1999) |
| Methyl-CpG-binding domain protein 2 (MBD2) | MBD domain | FAT? | Decreases MBD2 association with HDAC1 and methyl CpG site; binding, co-IP | Luo et al. (2009) |
| Nephrocystin-1, -4 | N-ter, SH3 | PR3 | Complex with p130Cas, tensin | Benzing et al. (2001); Mollet et al. (2005) |
| Paxillin | LD domains | FAT | Hiregowdara et al. (1997); Matsuya et al. (1998); Zheng et al. (1998); Ivankovic-Dikic et al. (2000); Anfosso et al. (2001); Vanarotti et al. (2014) | |
| Leupaxin (LIM domains, LD, similar to paxillin) | LD | FAT | Complex with PTP-PEST; binding, co-IP | Lipsky et al. (1998); Sahu et al. (2007); Vanarotti et al. (2016) |
| HIC-5 (LIM domains, LD, similar to paxillin) | LD | FAT | Binding, co-IP | Matsuya et al. (1998); Wang et al. (2002) |
| PLC-γ1, -γ2 | C-ter SH2 and SH3 | pTyr and/or PR | Complex with β3 integrin, PLC-γ, phosphatidylinositol 3-kinase | Nakamura I. et al. (2001) |
| Protein kinase MAP4K4 (mitogen-activated protein kinase 4) | C-terminal citron homology domain (CNH) | FERM | Role in glioma cell migration | Loftus et al. (2013) |
| PTK Abl | SH2 | pTyr881 | Complex with pl90 RhoGAP (pi90), RasGAP, c-Abl, pl30cas, paxillin. | Zrihan-Licht et al. (2004) |
| PTK Fyn / p59-Fyn | SH2 | pTyr402 | Ganju et al. (1997); Qian et al. (1997); Marie-Cardine et al. (1999); Katagiri et al. (2000); Li and Gotz (2018) | |
| PTK Lck / p56-Lck | SH2 | Co-IP | Ganju et al. (1997); Qian et al. (1997) | |
| PTK Lyn / p56-Lyn | SH2? | Yamasaki et al. (2001) | ||
| PTK Src / p60-Src | SH2, SH3? | pTyr402, PR1? | Dikic et al. (1996); Duong et al. (1998); Kumar et al. (1999); Keely et al. (2000); Sanjay et al. (2001); Faccio et al. (2003); Lakkakorpi et al. (2003); Bruzzaniti et al. (2009); Hum et al. (2014) | |
| PTK Yes (c-Yes / p61-Yes) | SH2? | Pancreatic acinar cells | Sancho et al. (2012) | |
| PTK ZAP-70 | SH2? | Katagiri et al. (2000) | ||
| PTP non-receptor type 11 (SHPTP2 / SHP2) | Not the SH2 domain | pTyr402 | Pyk2 is a substrate for SHPTP2 in response to dexamethasone and IL-6 | Chauhan et al. (2000) |
| PTP non-receptor type 5 / Striatum-enriched protein-tyrosine phosphatase (PTPN5 / STEP) | PR2 and KIM domains of STEP61 | 671–694 | Dephosphorylates pY402 | Xu et al. (2012) |
| Proto-oncogene vav (VAV1) | SH3 (605–662) and SH3 (786–844) | PR? | Complex with ZAP-70 | Katagiri et al. (2000) |
| FAK family kinase–interacting protein of 200 kD (FIP200) / RB1-inducible coiled-coil protein 1 | C-ter | Kinase domain | Yeast 2-hybrid, co-IP, FIP200 inhibits Pyk2 | Ueda et al. (2000) |
| RNA-binding protein EWS (EWSR1) | N-ter | 656–797 | Co-IP, pull-down | Felsch et al. (1999) |
| SAP90/PSD-95-associated protein 3 (SAPAP3) / Disks large-associated protein 3 (DAP3) | C-ter (436–977) | Yeast 2-hybrid (FAK), GST-pulldown | Bongiorno-Borbone et al. (2005) | |
| Src kinase-associated phosphoprotein 2 (SKAP2) / Pyk2/RAFTK-associated protein (PRAP) | SH3 | C-ter region | Yeast 2-hybrid, co-IP, may associate Pyk2 and α-synuclein | Takahashi et al. (2003) |
| Suppressor of cytokine signaling 2 (SOCS2); SOCS3 | SH2 | pY402 | SOCS2 induces proteasome-mediated degradation pPyk2 via ubiquitination | Zhang et al. (2008); Lee et al. (2010) |
Co-IP, co-immunoprecipitation; GST, glutathione-S transferase; KIM, kinase interaction motif; LD, leucine-aspartic acid motif; LIM, acronym of the three genes in which the domain was first identified: LIN-11, Isl-1 and MEC-3; PR, proline-rich motif; PTK, protein tyrosine kinase; PTP, protein tyrosine phosphatase; SH2, SH3, Src-homology 2, 3. Question marks indicate interacting domains that are not directly identified but very likely involved based on similarity with other characterized interactions.