Cerebellar beta 2-chimaerin, a GTPase-activating protein for p21 ras-related rac is specifically expressed in granule cells and has a unique N-terminal SH2 domain.
beta-Chimaerin, a 30-kDa GTPase-activating protein (GAP) for the p21 Ras-related Rac, is expressed specifically in late stage spermatocytes (Leung, T., How, B.-E., Manser, E., and Lim, L. (1993) J. Biol. Chem. 268, 3813-3816). Using antibodies raised against beta-chimaerin, we detected a major 46-kDa RacGAP in the rat cerebellum. With beta-chimaerin cDNA as a probe and using polymerase chain reaction, cDNAs from both human and rat cerebellum were isolated. The human and rat cDNAs encoded sequences containing cysteine-rich and GAP domains identical to those of testis beta-chimaerin. The cDNAs also encoded an additional N-terminal SH2 (Src homology 2) domain, probably derived from the beta-chimaerin gene by alternate splicing. This SH2 domain of the predicted 54-kDa protein was strikingly similar to that of alpha 2-chimaerin, including replacement by glutamic acid of the invariant tryptophan present at the start of other SH2 domains. The SH2 domains of alpha- and beta-chimaerin thus represent a subset of SH2 domains. The cerebellar beta-chimaerin (beta 2-) is expressed mainly in granule cells and exhibits postnatal developmental increases. beta 2-Chimaerin was enriched in particulate/synaptosomal fractions. In the mouse weaver mutant lacking mature granule cells, there is a corresponding decrease in beta 2-chimaerin, which could well serve as a marker of granule cell differentiation.
Leung
T
T
Institute of Molecular and Cell Biology, National University of Singapore.
How
B E
BE
Manser
E
E
Lim
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D013574:Synaptosomes / Q000378:metabolism; D020744:rac GTP-Binding Proteins; D020703:ras GTPase-Activating Proteins
D018076:DNA, Complementary; D020690:GTPase-Activating Proteins; D009363:Neoplasm Proteins; D011506:Proteins; C079844:beta-chimaerin; D020703:ras GTPase-Activating Proteins; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins