LIS1 is a microtubule-associated phosphoprotein.
Lissencephaly, a severe brain malformation, may be caused by mutations in the LIS1 gene. LIS1 encodes a microtubule-associated protein (MAP) that is also part of the enzyme complex, platelet-activating factor acetylhydrolase. LIS1 is also found in a complex with two protein kinases; a T-cell Tat-associated kinase, which contains casein-dependent kinase (CDK) activating kinase (CAK), as well as CAK-inducing activity, and with a spleen protein-tyrosine kinase similar to the catalytic domain of p72syk. As phosphorylation is one of the ways to control cellular localization and protein-protein interactions, we investigated whether LIS1 undergoes this post-translational modification. Our results demonstrate that LIS1 is a developmentally regulated phosphoprotein. Phosphorylated LIS1 is mainly found in the MAP fraction. Phosphoamino acid analysis revealed that LIS1 is phosphorylated on serine residues. Alkaline phosphatase treatment reduced the number of visible LIS1 isoforms. In-gel assays demonstrate a 50-kDa LIS1 kinase that is enriched in microtubule-associated fractions. In vitro, LIS1 was phosphorylated by protein kinase CKII (casein kinase II), but not many other kinases that were tested. We suggest that LIS1 activity may be regulated by phosphorylation.
Sapir
T
T
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Cahana
A
A
Seger
R
R
Nekhai
S
S
Reiner
O
O
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001921:Brain / Q000196:embryology*; D047390:Casein Kinase II; D002417:Cattle; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010741:Phospholipases A; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D042925:Positive Transcriptional Elongation Factor B; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse