Page 23 - Essential Haematology

Chapter 1 Haemopoiesis / 9

Growth
factor

Plasma membrane
PI3Kinase

JAK
AKT
JAK
Blocked
STATs RAS
apoptosis
RAF
Nucleus
Active STAT dimers MAP kinase
MYC, FOS

M Gene
expression
Activation of
gene expression

G2 G1

E2F
S
Rb

p53

DNA damage

Figure 1.8 Control of haemopoiesis by growth factors. The factors act on cells expressing the corresponding

receptors. Binding of a growth factor to its receptor activates the JAK/STAT, MAPK and phosphatidyl - inositol
3 - kinase (PI3K) pathways (see Fig. 15.2 ) which leads to transcriptional activation of specifi c genes. E2F is a

transcription factor needed for cell transition from G1 to S phase. E2F is inhibited by the tumour suppressor
gene Rb (retinoblastoma) which can be indirectly activated by p53. The synthesis and degradation of different
cyclins (Fig. 1.10 ) stimulates the cell to pass through the different phases of the cell cycle. The growth factors
may also suppress apoptosis by activating AKT (protein kinase B).