The human stress-activated protein kinase-interacting 1 gene encodes JNK-binding proteins.
The orthologous proteins of the stress-activated protein kinase-interacting 1 (Sin1) family have been implicated in several different signal transduction pathways. In this study, we have investigated the function of the full-length human Sin1 protein and a C-terminally truncated isoform, Sin1alpha, which is produced by alternative splicing. Immunoblot analysis using an anti-Sin1 polyclonal antibody showed that full-length Sin1 and several smaller isoforms are widely expressed. Sin1 was demonstrated to bind to c-Jun N-terminal kinase (JNK) in vitro and in vivo, while no interaction with p38- or ERK1/2-family MAPKs was observed. The Sin1alpha isoform could also form a complex with JNK in vivo. Despite localizing in distinct compartments within the cell, both Sin1 and Sin1alpha co-localized with JNK, suggesting that the Sin1 proteins could recruit JNK. Over-expression of full-length Sin1 inhibited the activation of JNK by UV-C in DG75 cells, as well as basal JNK-activity in HEK293 cells. These data suggest that the human Sin1 proteins may act as scaffold molecules in the regulation of signaling by JNK.
Schroder
Wayne
W
The Queensland Institute of Medical Research, 300 Herston Road, Brisbane 4029, Australia. wayneS@qimr.edu.au
Bushell
Gillian
G
Sculley
Tom
T
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C493277:MAPKAP1 protein, human; D020033:Protein Isoforms; D048031:JNK Mitogen-Activated Protein Kinases