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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 103

Module 2: Figure JAK/STAT heterogeneity

TYPE I CYTOKINES
JAK1 STAT5a, STAT5b
IL-2, IL-7,IL-9, IL-15
JAK3 STAT3
JAK1
IL-4 JAK3 STAT6

JAK1,JAK2
IL-13 STAT6
Tyk2
IL-3, IL-5, G-CSF, JAK2 STAT5a, STAT5b
GM-CSF
IL-6, IL-11, OSM JAK1,JAK2 STAT3
CNTF, LIF, CT-1 Tyk2

IL-12 JAK2, Tyk2 STAT4
Growth JAK2 STAT5a, STAT5b
hormone STAT3
Prolactin JAK2 STAT5a, STAT5b

Erythropoietin JAK2 STAT5a, STAT5b

Thrombopoietin JAK2 STAT5a, STAT5b

TYPE II CYTOKINES
IFN IFN JAK1, Tyk2 STAT1, STAT2

IFN JAK1, Tyk2 STAT1

IL-10 JAK1, Tyk2 STAT3

Heterogeneity of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) combinations used by different cytokine receptors.
The cytokines acting on cell-surface receptors (blue and mauve boxes) activate different combinations of Janus kinases (JAKs) and signal transducers
and activators of transcription (STATs). CNTF, ciliary neurotrophic factor; GCSF, granulocyte colony-stimulating factor; IFN, interferon; IL, interleukin;
LIF, leukaemia inhibitory factor; OSM, oncostatin M. The organization of some of the type I cytokine receptors is shown in Module 1: Figure type I
cytokine receptors.

SCID was found in patients carrying mutations in JAK3. growth factor β (TGF-β) superfamily, which are cytokines
SCID resulted from a dramatic reduction in the number of that regulate many cellular functions such as proliferation,
T cells, highlighting the important role for this signalling apoptosis, extracellular matrix formation and angiogen-
pathway in lymphocyte development. esis. In addition, they play a critical role in controlling
One of the functions of STAT3 is to stimulate the tran- events during early development and cell differentiation.
scription of genes that code for anti-apoptotic factors such There is an extensive Smad signalling toolkit,and themany
as Bcl-2 and the inhibitor of apoptosis (IAP) family of components can be mixed and matched to assemble a large
proteins. variety of Smad signalling pathways. The domain struc-
JAKs have also been implicated in certain forms of ma- ture of the Smad family illustrates their multifunctional
lignant transformation such as Sezary’s syndrome, v-Abl- roles in the Smad signalling mechanism that functions to
transformed cells and in some leukaemias. transfer information from activated receptors on the cell
surface to gene targets in the nucleus. This signalling mech-
anism has two main components. Firstly, there is a process
Smad signalling pathway of transforming growth factor β (TGF-β) receptor ac-
This signalling pathway takes its name from the Smads, tivation, which is responsible for activating the Smads.
which are a collection of intracellular signalling molecules Secondly, there is the Smad activation of transcription.
that act collectively to transfer information from cell- There are a number of mechanisms for the modulation of
surface receptors into the nucleus. As such, some of the Smad signalling. Transforming growth factor β (TGF-β)
Smads function as transcription factors, whereas oth- inhibition of cell proliferation is one of the major functions
ers either facilitate or inhibit this transcriptional activ- of the Smad signalling pathway. It plays an important role
ity. These Smads mediate the action of the transforming in the differentiation of intestinal cells. Alterations in the

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