Signaling through the interaction of membrane-restricted stem cell factor and c-kit receptor kinase: Genetic evidence for a differential role in erythropoiesis

Reuben Kapur, Manus Majumdar, Xiangli Xiao, Monica McAndrews-Hill, Karen Schindler, David A. Williams

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Mutations of the receptor tyrosine kinase c-kit or its ligand stem cell factor (SCF), which is encoded as a soluble and membrane-associated protein by the Steel gene in mice, lead to deficiencies of germ cells, melanocytes, and hematopoiesis, including the erythroid lineage. In the present study, we have used genetic methods to study the role of membrane or soluble presentation of SCF in hematopoiesis. Bone marrow-derived stromal cells expressing only a membrane-restricted (MR) isoform of SCF induced an elevated and sustained tyrosine phosphorylation of both c-kit and erythropoietin receptor (OPO-R) and significantly greater proliferation of an erythrocytic progenitor cell line compared with stromal cells expressing soluble SCF. Transgene expression of MR-SCF in Steel-dickie (Sl(d)) mutants resulted in a significant improvement in the production of red blood cells, bone marrow hypoplasia, and runting. In contrast, overexpression of the full-length soluble form of SCF transgene had no effect on either red blood cell production or runting but corrected the myeloid progenitor cell deficiency seen in these mutants. These data provide the first evidence of differential functions of SCF isoforms in vivo and suggest an abnormal signaling mechanism as the cause of the severe anemia seen in mutants of the Sl-gene.

Original languageEnglish (US)
Pages (from-to)879-889
Number of pages11
JournalBlood
Volume91
Issue number3
StatePublished - Feb 1 1998
Externally publishedYes

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Proto-Oncogene Proteins c-kit
Stem Cell Factor
Erythropoiesis
Phosphotransferases
Membranes
Cells
Steel
Hematopoiesis
Transgenes
Protein Isoforms
Bone
Blood
Genes
Erythrocytes
Erythropoietin Receptors
Myeloid Progenitor Cells
Phosphorylation
Melanocytes
Receptor Protein-Tyrosine Kinases
Stromal Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Signaling through the interaction of membrane-restricted stem cell factor and c-kit receptor kinase : Genetic evidence for a differential role in erythropoiesis. / Kapur, Reuben; Majumdar, Manus; Xiao, Xiangli; McAndrews-Hill, Monica; Schindler, Karen; Williams, David A.

In: Blood, Vol. 91, No. 3, 01.02.1998, p. 879-889.

Research output: Contribution to journalArticle

Kapur, Reuben ; Majumdar, Manus ; Xiao, Xiangli ; McAndrews-Hill, Monica ; Schindler, Karen ; Williams, David A. / Signaling through the interaction of membrane-restricted stem cell factor and c-kit receptor kinase : Genetic evidence for a differential role in erythropoiesis. In: Blood. 1998 ; Vol. 91, No. 3. pp. 879-889.
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