Table 2 Comparison of primary structures of proposed CDK5 substrates
Substrate | Phosphorylated sequence | Proposed effect of phosphorylation |
|---|---|---|
CLASS 1 (Lys/Arg residues N- and C-terminal) | ||
CRMP2 | PASSAKTSPAKQQ (S522) | Axon Growth and development |
CRMP4 | PAGSARGSPTRP (S522) | Myelin dependent axon outgrowth |
Synaptojanin | EAPKSPGTTRKD (S1144) | Inhibits interaction with endophilin 1 |
Tau | TPPKSPSSAKS (S235/AT180) | Makes tau a better substrate for GSK3 |
Tyr Hydroxylase-1 | YTPTPRSPRFIGRR (S31) | Makes protein more stable |
ATM | CLCIHTKHTPNKIAS (mouse S793) | Activation of ATM- apoptosis |
Bcl-2 | EMAARTSPLRPLV (mouse S80) | Induces neuronal survival |
Cdh-1 | SQKLLRSPRKPTRK (mouse S163) | Stabilises cyclin B1 |
mSDS3 (HDAC) | NKLKSPKRPASPSS (mouse S224) | Promotes dimerisation and activation |
PIK-A | RGKLSPRKGKSKTL (mouse S279) | Stimulates PI 3-kinase/Akt pathway |
Neurabin I | GKGGHSSPQRRMKPKEF (S95) | Regulates binding to F-actin |
CLASS 2 (Lys/Arg residues C-terminal only) | ||
DARPP32/PPP1R1B | PCAYTPPSLK (T75) | Phospho-DARPP32 inhibits PKA |
Inhibitor-1 | MEQDNSPRKIQFTVP (S6) | Regulates activity toward PP1 |
Dynamin I | SPTSSPTPQRRAPA (T778) | Regulates endocytosis |
Inhibitor-1 | TLAMSPRQRKKMTRITP (S66) | Regulates activity toward PP1 |
SPAR | LGAATSSPRSGPGKE (S1328) | Regulates synaptic plasticity |
Cdh-1 | ANSPVSSPSKHGDR (mouse S40) | Stabilises cyclin B1 |
Mef2A | SEPISPPRDRMTP (mouse 406) | Regulates apoptosis |
Mek1 | GDAAETPPRPRTP (mouse T283) | Inhibits MEK signalling |
p53 | CTSASPPQKKKPL (mouse S314) | Regulates apoptosis of PC12 cells |
PLD2 | FAVTHSPAREAA (mouse S134) | Activation (part of EGF action) |
STAT3 | IDLPMSPRTLDS (mouse S727) | Upregulated transcriptional activity |
Stathmin (Leukemia-associated phosphoprotein p18) | VPDFPLSPPKKKD (mouse S41) | Stabilises protein |
Talin | EDSVSPKKSTVLQ (mouse S425) | Regulates binding to smurf1/cell migration |
CLASS 3 (Lys/Arg residues N-terminal only) | ||
Doublecortin | STPKSKQSPISTPT (mouse S332) | Unclear |
CLASS 4 (No Lys/Arg residues) | ||
FAK | EGFYPSPQHMVQT (mouse S766) | Critical for neuronal migration |
p53 | PEDILPSPHCMDDL (mouse S33) | Regulates apoptosis of PC12 cells |
PSD95 | LPNQANSPPVIV (S35) | Regulates structure of synapse |