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Table 2 Comparison of primary structures of proposed CDK5 substrates

From: Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis

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
  1. Primary sequence surrounding proposed CDK5 target residues; substrates are classified by presence of Arg/Lys residues (underlined) within 5 amino acids N-terminal or C-terminal to the phosphorylated residue which is always N-terminal to a proline