Differences in c-Jun N-terminal kinase recognition and phosphorylation of closely related stathmin-family members.
Biochem Biophys Res Commun
; 446(1): 248-54, 2014 Mar 28.
Article
in En
| MEDLINE
| ID: mdl-24589734
ABSTRACT
The stathmin (STMN) family of tubulin-binding phosphoproteins are critical regulators of interphase microtubule dynamics and organization in a broad range of cellular processes. c-Jun N-terminal kinase (JNK) signalling to STMN family proteins has been implicated specifically in neuronal maturation, degeneration and cell stress responses more broadly. Previously, we characterized mechanisms underlying JNK phosphorylation of STMN at proline-flanked serine residues (Ser25 and Ser38) that are conserved across STMN-like proteins. In this study, we demonstrated using in vitro kinase assays and alanine replacement of serine residues that JNK phosphorylated the STMN-like domain (SLD) of SCG10 on Ser73, consistent with our previous finding that STMN Ser38 was the primary JNK target site. In addition, we confirmed that a JNK binding motif ((41)KKKDLSL(47)) that facilitates JNK targeting of STMN is conserved in SCG10. In contrast, SCLIP was phosphorylated by JNK primarily on Ser60 which corresponds to Ser25 on STMN. Moreover, although the JNK-binding motif identified in STMN and SCG10 was not conserved in SCLIP, JNK phosphorylation of SCLIP was inhibited by a substrate competitive peptide (TI-JIP) highlighting kinase-substrate interaction as required for JNK targeting. Thus, STMN and SCG10 are similarly targeted by JNK but there are clear differences in JNK recognition and phosphorylation of the closely related family member, SCLIP.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mitogen-Activated Protein Kinase 8
/
Stathmin
/
Membrane Proteins
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2014
Document type:
Article
Affiliation country: