The Kit ligand (KL)/Kit receptor pair functions in hematopoiesis, gametogenesis, and melanogenesis. KL is encoded at the murine steel ( Sl ) locus and encodes a membrane growth factor which may be proteolytically processed to produce soluble KL. The membrane-associated form of KL is critical in mediating Kit function in vivo. Evidence for a role of cytoplasmic domain sequences of KL comes from the Sl 17H mutation, a splice site mutation that replaces the cytoplasmic domain with extraneous amino acids. Using deletion mutants and the Sl 17H allele, we have investigated the role of the cytoplasmic domain sequences of KL in biosynthetic processing and cell surface presentation. The normal KL protein products are processed for cell surface expression, where they form dimers. Both Sl 17H and the cytoplasmic deletion mutants of KL were processed to the cell surface; however, the rate of transport and protein stability were affected by the mutations. Deletion of cytoplasmic domain sequences of KL did not affect dimerization of KL. In contrast, dimerization of the Sl 17H protein was reduced substantially. In addition, we have characterized the hematopoietic cell compartment in Sl 17H mutant mice. The Sl 17H mutation has only minor effects on hematopoiesis. Tissue and peritoneal mast cell numbers were reduced in mutant mice as well as in myeloid progenitors. Interestingly, long-term bone marrow cultures from Sl 17H mice did not sustain the long-term production of hematopoietic cells. In addition, homing of normal hematopoietic progenitors to the spleen of irradiated Sl 17H / Sl 17H recipient mice was diminished in transplantation experiments, providing evidence for a role of Kit in homing or lodging. These results demonstrate that the membrane forms of KL exist as homodimers on the cell surface and that dimerization may play an important role in KL/Kit-mediated juxtacrine signaling. Footnotes Support by grants from the American Cancer Society and the National Institutes of Health is acknowledged. Abbreviations used in this paper: BFU-E burst-forming unit–erythroid BMMC bone marrow–derived mast cell CFU-GEMM CFU-granulocyte erythroid megakaryocyte macrophage CFU-S CFU-spleen endo endoglycosidase ER endoplasmic reticulum KL Kit ligand Sl steel VLA very late antigen W white-spotting WBC white blood cell Submitted: 21 November 1997 Revision received 9 February 1998
End of preview. The entire article is 11 pages. To view the full-text, please rent this article to continue.
/lp/rockefeller-university-press/role-of-dimerization-of-the-membrane-associated-growth-factor-kit-pehJL0f02T
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Role of Dimerization of the Membrane-associated Growth Factor Kit Ligand in Juxtacrine Signaling: The Sl17H Mutation Affects Dimerization and Stability—Phenotypes in Hematopoiesis
Tajima, Youichi; Huang, Eric J.; Vosseller, Keith; Ono, Masao; Moore, Malcolm A.S.; Besmer, Peter
Follow The Journal of Experimental Medicine
, Volume 187 (9): 1451
Rockefeller University Press – May 4, 1998
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
