JAK3: Expression and mapping to chromosome 19p12-13.1

M. G. Safford, M. Levenstein, E. Tsifrina, S. Amin, A. L. Hawkins, C. A. Griffin, C. I. Civin, Donald Small

Research output: Contribution to journalArticle

Abstract

We cloned JAK3, the most recently described member of the JAK family of intracellular tyrosine kinases, from normal human CD34+ RNA. JAK3 is involved in the signal transduction pathways of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors by association with their common γ-chain (γ(c)). JAK3 is critical to lymphoid development, as recently established by the linking of mutations in JAK3 to a subgroup of patients with SCID and the generation of JAK3-null mice with severe disruptions in normal lymphocytic development. However, JAK3 expression is not restricted to the lymphocytic compartment-of bone marrow but is found in a wide range of tissues of both hematopoietic and non-hematopoietic origin. Northern blot analysis indicates that JAK3 is also expressed in adult placenta, lung, liver, kidney, pancreas, spleen, thymus, ovary, and small intestine. RNAse protection assays and RT-PCR indicate that JAK3 is expressed in a variety of leukemic-derived hematopoietic cell lines with myeloid and/or lymphoid phenotypes. In normal human bone marrow, JAK3 is expressed in the CD34+/lineage- fraction, which is highly enriched in hematopoietic stem/progenitor cells. In addition, we found a splice variant of JAK3 which is formed by the splicing of JAK3 with exon II of the leydig insulin-like (LEY I-L) hormone. RT-PCR and RNAse protection assay analyses indicate that this variant (termed I-JAK3) is normally expressed in almost all hematopoietic and non-hematopoietic tissues shown to express JAK3. Using fluorescence in situ hybridization we have localized JAK3 to 19p12-13.1, the same region of chromosome 19 to which the LEY I-L hormone maps (19p12-13.2).

Original languageEnglish (US)
Pages (from-to)374-386
Number of pages13
JournalExperimental Hematology
Volume25
Issue number5
StatePublished - 1997

Fingerprint

Chromosome Mapping
Hematopoietic Stem Cells
Interleukin-15 Receptors
Bone Marrow
Interleukin-9
Hormones
Insulin
Chromosomes, Human, Pair 19
Interleukin-7
Polymerase Chain Reaction
Fluorescence In Situ Hybridization
Interleukin-4
Northern Blotting
Protein-Tyrosine Kinases
Thymus Gland
Placenta
Small Intestine
Interleukin-2
Pancreas
Ovary

Keywords

  • 19p12-13.1-Leydig insulin-like hormone
  • CD34
  • Hematopoietic stem cell
  • JAK3
  • Signal transduction
  • Tyrosine kinase

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Safford, M. G., Levenstein, M., Tsifrina, E., Amin, S., Hawkins, A. L., Griffin, C. A., ... Small, D. (1997). JAK3: Expression and mapping to chromosome 19p12-13.1. Experimental Hematology, 25(5), 374-386.

JAK3 : Expression and mapping to chromosome 19p12-13.1. / Safford, M. G.; Levenstein, M.; Tsifrina, E.; Amin, S.; Hawkins, A. L.; Griffin, C. A.; Civin, C. I.; Small, Donald.

In: Experimental Hematology, Vol. 25, No. 5, 1997, p. 374-386.

Research output: Contribution to journalArticle

Safford, MG, Levenstein, M, Tsifrina, E, Amin, S, Hawkins, AL, Griffin, CA, Civin, CI & Small, D 1997, 'JAK3: Expression and mapping to chromosome 19p12-13.1', Experimental Hematology, vol. 25, no. 5, pp. 374-386.
Safford MG, Levenstein M, Tsifrina E, Amin S, Hawkins AL, Griffin CA et al. JAK3: Expression and mapping to chromosome 19p12-13.1. Experimental Hematology. 1997;25(5):374-386.
Safford, M. G. ; Levenstein, M. ; Tsifrina, E. ; Amin, S. ; Hawkins, A. L. ; Griffin, C. A. ; Civin, C. I. ; Small, Donald. / JAK3 : Expression and mapping to chromosome 19p12-13.1. In: Experimental Hematology. 1997 ; Vol. 25, No. 5. pp. 374-386.
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AB - We cloned JAK3, the most recently described member of the JAK family of intracellular tyrosine kinases, from normal human CD34+ RNA. JAK3 is involved in the signal transduction pathways of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors by association with their common γ-chain (γ(c)). JAK3 is critical to lymphoid development, as recently established by the linking of mutations in JAK3 to a subgroup of patients with SCID and the generation of JAK3-null mice with severe disruptions in normal lymphocytic development. However, JAK3 expression is not restricted to the lymphocytic compartment-of bone marrow but is found in a wide range of tissues of both hematopoietic and non-hematopoietic origin. Northern blot analysis indicates that JAK3 is also expressed in adult placenta, lung, liver, kidney, pancreas, spleen, thymus, ovary, and small intestine. RNAse protection assays and RT-PCR indicate that JAK3 is expressed in a variety of leukemic-derived hematopoietic cell lines with myeloid and/or lymphoid phenotypes. In normal human bone marrow, JAK3 is expressed in the CD34+/lineage- fraction, which is highly enriched in hematopoietic stem/progenitor cells. In addition, we found a splice variant of JAK3 which is formed by the splicing of JAK3 with exon II of the leydig insulin-like (LEY I-L) hormone. RT-PCR and RNAse protection assay analyses indicate that this variant (termed I-JAK3) is normally expressed in almost all hematopoietic and non-hematopoietic tissues shown to express JAK3. Using fluorescence in situ hybridization we have localized JAK3 to 19p12-13.1, the same region of chromosome 19 to which the LEY I-L hormone maps (19p12-13.2).

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