Kiz-1, a protein with LIM zinc finger and kinase domains, is expressed mainly in neurons.
The olfactory epithelium is the only neuronal tissue capable of generating new neurons during adult life and hence must express genes responsible for this phenomenon. Therefore, we have used mRNA from immortalized olfactory epithelial cells to search for novel protein tyrosine kinases by polymerase chain reaction, using as primers conserved sequences from the catalytic domain of known kinase genes. A full-length complementary DNA clone corresponding to one such polymerase chain reaction product was isolated and sequenced. This complementary DNA, designated Kiz-1, encodes a protein containing two prominent domains; the NH2-terminal region contains a cysteine/histidine-rich moiety previously identified as a zinc-finger domain in proteins of the LIM family, while the COOH-terminus contains a kinase domain. Kiz-1 is expressed mainly in the brain of adult mice but also in a range of cultured cell lines, regardless of their tissue of origin. Immunohistochemical studies on adult mouse brain demonstrated that Kiz-1 is expressed exclusively in neurons, not in astrocytes or oligodendrocytes. In the developing embryo, however, Kiz-1 is expressed in all tissues. In COS cells transfected with Kiz-1 complementary DNA and in the immortalized olfactory epithelial cells, Kiz-1 was found mainly in the cytoplasm, but in neurons of the adult brain, it resided also in the nucleus. Two Kiz-1 mRNA species are expressed in cell lines as well as in the murine and human brain. One transcript lacks a region of 60 nucleotides, which lies within the catalytic domain of the kinase and is encoded by a separate exon. Our results suggest that Kiz-1 may play distinct roles in dividing cells and in differentiated neurons.
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
O
O
Bernard
S
S
Ganiatsas
G
G
Kannourakis
R
R
Dringen
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004847:Epithelial Cells; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D054461:Lim Kinases; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D009833:Olfactory Pathways / Q000166:cytology; D009928:Organ Specificity; D010770:Phosphotransferases / Q000235:genetics*; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017422:Sequence Analysis, DNA; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D010770:Phosphotransferases; D011494:Protein Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D017346:Protein Serine-Threonine Kinases