Nerve injury-associated kinase: a sterile 20-like protein kinase up-regulated in dorsal root ganglia in a rat model of neuropathic pain.
Partial injury of the rat sciatic nerve elicits a variety of characteristic chemical, electrophysical and anatomical changes in primary sensory neurons and constitutes a physiologically relevant model of neuropathic pain. To elucidate molecular mechanisms that underlie the physiology of neuropathic pain, we have used messenger RNA differential display to identify genes that exhibit increased ipsilateral expression in L4/5 dorsal root ganglia, following unilateral partial ligation of the rat sciatic nerve. One set of partial complementary DNA clones identified in this screen was found to encode a protein kinase, nerve injury-associated kinase. Cloning of the full-length human nerve injury-associated kinase complementary DNA, together with recombinant expression analysis, reveal nerve injury-associated kinase to be a functional member of a subgroup of sterile 20-like protein kinases characterised by the presence of a putative carboxy terminal autoregulatory domain. Induction of nerve injury-associated kinase expression in dorsal root ganglia in the rat neuropathic pain model was confirmed by quantitative reverse transcription-polymerase chain reaction, and RNA in situ hybridization analysis revealed enhanced levels of nerve injury-associated kinase within neurons.Together, our data implicate nerve injury-associated kinase as a novel upstream component of an intracellular signalling cascade that is up-regulated in dorsal root ganglia neurons in response to sciatic nerve injury.
Rausch
O
O
Department of Neurology, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park North, Essex, CM19 5AW, Harlow, UK.
Newton
R A
RA
Bingham
S
S
Macdonald
R
R
Case
C P
CP
Sanger
G J
GJ
Lawson
S N
SN
Reith
A D
AD
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001483:Base Sequence / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020869:Gene Expression Profiling; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000378:metabolism* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011494:Protein Kinases / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015854:Up-Regulation / Q000502:physiology
D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C420464:sterile 20-like protein kinase nerve injury-associated kinase; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae