Cloning of an Interleukin-3 Receptor Gene: a Member of a Distinct Receptor Gene Family

Itoh, Naoto; Yonehara, Shin; Schreurs, Jolanda; Gorman, Daniel M.; Maruyama, Kazuo; Ishii, Ayano; Yahara, Ichiro; Arai, Kohei; Miyajima, Atsushi

doi:10.1126/science.2404337

Cited by 403 publications

(153 citation statements)

References 36 publications

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“…The IL-3 and GM-CSF genes located on the 5q region of chromosome 5 has been associated with hematopoietic malignancies, underlining the importance of these cytokines in hematopoietic signaling (Blalock et al, 1999). The receptors for these cytokines have unique ligand binding-alpha chains and share the common beta (gp140) signal transducing subunit (Itoh et al, 1990;Murata et al, 1992;Gearing et al, 1989;Hayashida et al, 1990). In this review, we will examine in detail, the signal transduction mediated by IL-3, via its speci®c receptor, the IL-3R.…”

Section: The Gp140 Familymentioning

confidence: 99%

IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled

et al. 2000

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Hematopoiesis is the cumulative result of intricately regulated signal transduction cascades that are mediated by cytokines and their cognate receptors. Proper culmination of these diverse signaling pathways forms the basis for an orderly generation of di erent cell types and aberrations in these pathways is an underlying cause for diseases such as cancer. Over the past several years, downstream events initiated upon cytokine/ growth factor stimulation have been a major focus of biomedical research. As a result, several key concepts have emerged allowing a better understanding of the complex signaling processes. A group of novel transcription factors, termed signal transducers and activators of transcription (STATs) appear to orchestrate the downstream events propagated by cytokine/growth factor interactions with their cognate receptors. Until recently, the JAK proteins were considered to be the tyrosine kinases, which dictated the levels of phosphorylation and activation of STAT proteins, forming the basis of the JAK-STAT model. However, over the past few years, increasing evidence has accumulated which indicates that at least some of the STAT protein activation may be mediated by members of the Src gene family following cytokine/growth factor stimulation. Studies have demonstrated that the Src-family of tyrosine kinases can phosphorylate and activate certain STAT proteins, in lieu of JAK kinases. In such a scenario, JAK kinases may be more crucial to phosphorylation of the cytokine/growth factor receptors and in the process create docking sites on the receptors for binding of SH2-containing proteins such as STATs, Src-kinases and other signaling intermediates. Tyrosine phosphorylation and activation of STAT proteins can be achieved either by JAKs or Src-kinases depending on the nature of STAT that is being activated. This forms the basis for the JAK-Src-STAT model proposed in this review. The concerted action of JAK kinases, members of the Src-kinase family and STAT proteins, leads to cell proliferation and cell survival, the end-point of the cytokine/growth factor stimulus.

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Section: The Gp140 Familymentioning

confidence: 99%

IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled

et al. 2000

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“…The Ly49Q cDNA with the FLAG tag at the N terminus was inserted into an eukaryotic expression vector pME18S and transfected into COS7 cells by electroporation (20). Expression of Ly49Q was analyzed by flow cytometry or Western blot analysis 48 h after transfection.…”

Section: Methodsmentioning

confidence: 99%

Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture

Toyama–Sorimachi

Tsujimura

Maruya

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Here, we identified and characterized a Ly49 family member, designated as Ly49Q. The Ly49q gene encodes a 273-aa protein with an immunoreceptor tyrosine-based inhibitory motif (ITIM) at the N terminus of its cytoplasmic domain. We show that the ITIM of Ly49Q can recruit SHP-2 and SHP-1 in a tyrosine phosphorylation-dependent manner. In contrast to other known members of the Ly49 family, Ly49Q was found not to be expressed on NK1.

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“…GH-R) (7), while in the latter case, a ligand-specific ␣-chain forms a high affinity receptor only in combination with a signal transducing ␤-chain, which is often shared among several ␣-chains (e.g. IL-3, 5 and GM-CSF) (8). In either situation, ligand binding to the receptor leads to activation of cytoplasmic tyrosine kinases of the Janus kinase (Jak) family, which associate with the receptor subunits through conserved box-1 and box-2 motifs within the membrane proximal part of the intracellular domain (9).…”

mentioning

confidence: 99%

A Novel Type I Cytokine Receptor Is Expressed on Monocytes, Signals Proliferation, and Activates STAT-3 and STAT-5

Ghilardi¹,

Li²,

Hongo³

et al. 2002

Journal of Biological Chemistry

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Cloning of an Interleukin-3 Receptor Gene: a Member of a Distinct Receptor Gene Family

Cited by 403 publications

References 36 publications

IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled

IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled

Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture

A Novel Type I Cytokine Receptor Is Expressed on Monocytes, Signals Proliferation, and Activates STAT-3 and STAT-5

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