BIM acts as a sentinel to check the integrity of the cytoskeleton. It exists as two variant proteins: BIM-EL and BIM-L. In healthy cells, these two isoforms are sequestered to the dynein motor complex on microtubules via the dynein light chain DLC1. JNK or MAPK8 releases BIM in response to UV irradiation by phosphorylation.
MAPK8 (JNK) phosphorylates BCL2L11 (BIM) on a DLC-binding motif (DKSTQTP), involved in dynein (DYNLL2 i.e. DLC1) binding and sequestration of BCL2L11 (BIM) to the cytoskeleton. Phosphorylated BCL2L11 dissociates from dynein. Three sites in BCL2L11 match the JNK consensus: S44, T56 and S58 in BCL2L11 isoform BimL (these residues correspond to S104, T116 and S118 in BCL2L11 isoform BimEL), and all sites appear to be phosphorylated by MAPK8 (JNK) both in vitro and in vivo (Lei and Davis 2003).
The following GTPase activating proteins (GAPs) were shown to bind RHOF and stimulate its GTPase activity, resulting in GTP to GDP hydrolysis and conversion of the active RHOF:GTP complex into the inactive RHOF:GDP complex (the study by Bagci et al. 2020 reported binding of GAPs to active RHOF without testing for RHOF-directed GAP activity and is cited as a supporting evidence): ARHGAP1 (Amin et al. 2016; supported by Bagci et al. 2020)
The following candidate RHOF GAPs were reported by Bagci et al. 2020 to bind active RHOF, but their RHOF-directed GAP activity has not been tested: ARHGAP5 (Bagci et al. 2020) ARHGAP12 (Bagci et al. 2020) ARHGAP21 (Bagci et al. 2020) ARHGAP32 (Bagci et al. 2020) ARHGAP39 (Bagci et al. 2020) DEPDC1B (Bagci et al. 2020) MYO9B (Bagci et al. 2020) PIK3R1 (Bagci et al. 2020) PIK3R2 (Bagci et al. 2020) SRGAP2 (Bagci et al. 2020) SYDE1 (Bagci et al. 2020)
The following GAPs were reported to not act on RHOF or were reported by Bagci et al. 2020 to not bind active RHOF without testing of their RHOF-directed GAP activity: ABR (Amin et al. 2016; Bagci et al. 2020) ARAP2 (Bagci et al. 2020) ARAP3 (Bagci et al. 2020) ARHGAP17 (Amin et al. 2016; Bagci et al. 2020) ARHGAP26 (Amin et al. 2016) ARHGAP29 (Bagci et al. 2020) ARHGAP31 (Bagci et al. 2020) ARHGAP35 (Amin et al. 2016); Bagci et al. 2020) ARHGAP42 (Bagci et al. 2020) BCR (Bagci et al. 2020) DLC1 (Amin et al. 2016) MYO9A (Bagci et al. 2020) OCRL (Lichter Konecki et al. 2006; Erdmann et al. 2007; Bagci et al. 2020) OPHN1 (Amin et al. 2016; Bagci et al. 2020) RACGAP1 (Amin et al. 2016; Bagci et al. 2020) STARD13 (Amin et al. 2016) STARD8 (Amin et al. 2016)
The following GTPase activating proteins (GAPs) were shown to bind RHOD and stimulate its GTPase activity, resulting in GTP to GDP hydrolysis and conversion of the active RHOD:GTP complex to the inactive RHOD:GDP complex (the study by Bagci et al. 2020 is cited as supporting evidence since it only examined binding of GAPs to active RHOD without testing for RHOD-directed GAP activity): ARHGAP1 (Amin et al. 2016; supported by Bagci et al. 2020) ARHGAP26 (Amin et al. 2016) ARHGAP32 (Paul et al. 2017; supported by Bagci et al. 2020) ARHGAP35 (Amin et al. 2016; supported by Bagci et al. 2020)
The following GAPs were shown to bind RHOD and stimulate its GTPase activity in some but not all studies or were shown by Bagci et al. 2020 to bind to active RHOD without testing for RHOD-directed GAP activity and are annotated as candidate RHOD GAPs: ARHGAP5 (Bagci et al. 2020) ARHGAP12 (Bagci et al. 2020) ARHGAP17 (Amin et al. 2016: RHOD directed GAP activity; Bagci et al. 2020: no binding to active RHOD) ARHGAP21 (Bagci et al. 2020) ARHGAP39 (Bagci et al. 2020) DEPDC1B (Bagci et al. 2020) PIK3R1 (Bagci et al. 2020) PIK3R2 (Bagci et al. 2020) RACGAP1 (Amin et al. 2016: RHOD directed GAP activity; Bagci et al. 2020: no binding to active RHOD)
The following GAPs do not act on RHOD or were shown by Bagci et al. 2020 to not bind to active RHOD: ABR (Amin et al. 2016; Bagci et al. 2020) ARAP2 (Bagci et al. 2020) ARAP3 (Bagci et al. 2020) ARHGAP29 (Bagci et al. 2020) ARHGAP31 (Bagci et al. 2020) ARHGAP42 (Bagci et al. 2020) BCR (Bagci et al. 2020) DLC1 (Amin et al. 2016) MYO9A (Bagci et al. 2020) MYO9B (Bagci et al. 2020) OPHN1 (Amin et al. 2016; Bagci et al. 2020) SRGAP2 (Bagci et al. 2020) STARD13 (Amin et al. 2016) STARD8 (Amin et al. 2016) SYDE1 (Bagci et al. 2020)
The following GTPase activating proteins (GAPs) were shown to bind RHOQ and stimulate its GTPase activity, resulting in GTP to GDP hydrolysis and conversion of the active RHOQ:GTP complex to the inactive RHOQ:GDP complex (the study by Bagci et al. 2020 examined binding of GAPs to constitutively active RHOQ mutant, without assessing RHOQ-directed GAP activity and is cited as supporting evidence): ARHGAP1 (Amin et al. 2016; supported by Bagci et al. 2020) ARHGAP26 (Amin et al. 2016) DLC1 (Amin et al. 2016)
The following GAPs were shown to bind RHOQ and stimulate its GTPase activity in some but not all studies or were only shown by Bagci et al. 2020 to bind active RHOQ without testing for RHOQ-directed GAP activity and are annotated as candidate RHOQ GAPs: ARHGAP5 (Bagci et al. 2020) ARHGAP17 (Amin et al. 2016: RHOQ directed GAP activity; Bagci et al. 2020: no binding to active RHOQ) ARHGAP21 (Bagci et al. 2020) ARHGAP32 (Bagci et al. 2020) ARHGAP35 (Amin et al. 2016: RHOQ directed GAP activity; Bagci et al. 2020: no binding to active RHOQ) DEPDC1B (Bagci et al. 2020) OPHN1 (Amin et al. 2016: RHOQ directed GAP activity; Bagci et al. 2020: no binding to active RHOQ) SRGAP2 (Bagci et al. 2020) SYDE1 (Bagci et al. 2020)
The following GAPs do not act on RHOQ or were shown by Bagci et al. 2020 to not bind to active RHOQ, without testing for their RHOQ-directed GAP activity: ABR (Amin et al. 2016; Bagci et al. 2020) ARAP2 (Bagci et al. 2020) ARAP3 (Bagci et al. 2020) ARHGAP12 (Bagci et al. 2020) ARHGAP29 (Bagci et al. 2020) ARHGAP31 (Bagci et al. 2020) ARHGAP39 (Bagci et al. 2020) ARHGAP42 (Bagci et al. 2020) BCR (Bagci et al. 2020) MYO9A (Bagci et al. 2020) MYO9B (Bagci et al. 2020) OCRL (Bagci et al. 2020) RACGAP1 (Amin et al. 2016; Bagci et al. 2020) STARD13 (Amin et al. 2016) STARD8 (Amin et al. 2016)
The following GTPase activating proteins (GAPs) were shown to bind RHOJ and stimulate its GTPase activity, resulting in GTP to GDP hydrolysis and conversion of the active RHOJ:GTP complex into the inactive RHOJ:GDP complex (the high throughput study by Bagci et al. 2020 examined binding of GAPs to constitutively active RHOJ mutant without testing for RHOJ-directed GAP activity, and is cited as supporting evidence): ARHGAP1 (Amin et al. 2016; supported by Bagci et al. 2020) ARHGAP26 (Amin et al. 2016) ARHGAP35 (Amin et al. 2016; supported by Bagci et al. 2020)
The following GAPs were shown to bind RHOJ and stimulate its GTPase activity in some but not all studies or were shown by Bagci et al. 2020 to bind to constitutively active RHOJ mutant without testing for RHOJ-directed GAP activity and are annotated as candidate RHOJ GAPs: ARHGAP5 (Bagci et al. 2020) ARHGAP21 (Bagci et al. 2020) ARHGAP32 (Bagci et al. 2020) DEPDC1B (Bagci et al. 2020) OCRL (Bagci et al. 2020: binding to active RHOJ) OPHN1 (Amin et al. 2016: RHOJ directed GAP activity; Bagci et al. 2020: no binding to active RHOJ) PIK3R1 (Bagci et al. 2020) PIK3R2 (Bagci et al. 2020) SYDE1 (Bagci et al. 2020)
The following GAPs do not act on RHOJ or were shown by Bagci et al. 2020 to no bind to constitutively active RHOJ mutant and are thus unlikely to be RHOJ GAPs: ABR (Amin et al. 2016; Bagci et al. 2020) ARAP2 (Bagci et al. 2020) ARAP3 (Bagci et al. 2020) ARHGAP12 (Bagci et al. 2020) ARHGAP17 (Amin et al. 2016; Bagci et al. 2020) ARHGAP29 (Bagci et al. 2020) ARHGAP31 (Bagci et al. 2020) ARHGAP39 (Bagci et al. 2020) ARHGAP42 (Bagci et al. 2020) BCR (Bagci et al. 2020) DLC1 (Amin et al. 2016) MYO9A (Bagci et al. 2020) MYO9B (Bagci et al. 2020) RACGAP1 (Amin et al. 2016; Bagci et al. 2020) SRGAP2 (Bagci et al. 2020) STARD13 (Amin et al. 2016) STARD8 (Amin et al. 2016)
The following GTPase activating proteins (GAPs) were shown to bind RHOG and stimulate its GTPase activity, resulting in GTP to GDP hydrolysis and conversion of the active RHO:GTP complex into the inactive RHO:GDP complex: ARHGAP35 (Amin et al. 2016; supported by Bagci et al. 2020 by showing binding of ARHGAP35 to the constitutively active RHOG mutant)
The following GAPs were shown to bind RHOG and stimulate its GTPase activity in some but not all studies or were only shown to bind to constitutively active RHOG mutant without testing for the activation of the RHOG GTPase activity and are annotated as candidate RHOG GAPs: ARHGAP1 (Amin et al. 2016: RHOG directed GAP activity; Bagci et al. 2020: no binding to active RHOG) ARHGAP5 (Bagci et al. 2020: binding to active RHOG) ARHGAP21 (Bagci et al. 2020: binding to active RHOG) ARHGAP32 (Bagci et al. 2020: binding to active RHOG) ARHGAP39 (Bagci et al. 2020: binding to active RHOG) DEPDC1B (Bagci et al. 2020: binding to active RHOG) OPHN1 (Amin et al. 2016: RHOG directed GAP activity; Bagci et al. 2020: no binding to active RHOG) PIK3R1 (Bagci et al. 2020: binding to active RHOG)
The following GAPs were shown to either not act on RHOG or to not bind the constitutively active RHOG mutant in the high throughput screen by Bagci et al. 2020: ABR (Amin et al. 2016; Bagci et al. 2020) ARAP2 (Bagci et al. 2020) ARAP3 (Bagci et al. 2020) ARHGAP11B (Florio et al. 2015) ARHGAP12 (Bagci et al. 2020) ARHGAP17 (Amin et al. 2016; Bagci et al. 2020) ARHGAP26 (Amin et al. 2016) ARHGAP29 (Bagci et al. 2020) ARHGAP31 (Bagci et al. 2020) ARHGAP36 (Rack et al. 2014) ARHGAP42 (Bagci et al. 2020) BCR (Bagci et al. 2020) DLC1 (Amin et al. 2016) MYO9A (Bagci et al. 2020) MYO9B (Bagci et al. 2020) OCRL (Erdmann et al. 2007; Lichter Konecki et al. 2006; Bagci et al. 2020) PIK3R2 (Bagci et al. 2020) RACGAP1 (Amin et al. 2016; Bagci et al. 2020) SRGAP2 (Bagci et al. 2020) STARD13 (Amin et al. 2016) STARD8 (Amin et al. 2016) SYDE1 (Bagci et al. 2020)