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Vol. 50, Issue 1, 1-20, March 1998
Eppley Institute for Research in Cancer, University of Nebraska
Medical Center, Omaha, Nebraska
I. Introduction and Scope
II. Biology of Hematopoiesis: Brief Overview
A. The Hematopoietic Stem Cell
B. Control of Myeloid Differentiation by Colony-Stimulating Factors
and Other Cytokines
III. Overview of Cytokine Receptor Structure
A. Hematopoietic Growth Factor Receptors With Intrinsic Tyrosine
Kinase Activity
B. Cytokine Receptors Share Subunits and Lack Intrinsic Tyrosine
Kinase Activity
1. Receptors for interleukin-3, granulocyte-macrophage
colony-stimulating factor, and interleukin-5 share a common
subunit (c).
2. Interleukin-6 receptor subfamily and the glycoprotein 130 signal
transducer.
3. The interleukin-2 receptor subfamily shares a common 
chain
(c).
4. Single chain receptors.
C. Distinct Receptor Domains Transmit Proliferation and
Differentiation Signals
IV. Cytokine Receptors Activate Multiple Cytoplasmic Tyrosine
Kinase Families
A. Jak Family
B. Src Family
C. Fps/Fes Family
D. Tec/Btk Family
E. Syk/ZAP70 Family
V. Hematopoietic Cytokines Activate Multiple Downstream Signaling
Pathways
A. Tyrosine Kinase Effectors Share Src Homology 2 Domains
B. Ras/Raf/Mitogen-Activated Protein Kinase Pathway
1. Activation of Ras occurs downstream of tyrosine kinases.
2. Ras activation is mediated via guanine nucleotide exchange.
3. Shc: regulator of Ras and independent effector.
4. Ras transmits signals for proliferation in some contexts and
differentiation in others.
5. Ras stimulates the Raf/MEK/mitogen-activated protein kinase
pathway downstream.
C. Other Src Homology 2 Effectors
1. Vav: alternative route to small G-protein activation.
2. Stat transcription factors.
3. Terminating the signal: hematopoietic cell phosphatase.
VI. Phorbol Esters and Protein Kinase C
VII. Conclusions
Acknowledgments
References
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