Transmembrane Signalling


Surface protein receptors detect a wide variety of different external signal molecules, inducing a resulting change in the cytoplasmic domain of a receptor, which activates an associated response regulator to transcribe a specific gene. In this way, the cell responds appropriately and uniquely to specific signals.

Keywords: receptor; ligand; response regulator; second messenger; kinase

Figure 1.

Two‐component signal transduction system in bacteria. This is one of the most common signalling mechanisms in bacteria. Binding of an external ligand, for example a toxic compound, induces a conformational change in a sensor kinase receptor which is propagated through the membrane, through a piston‐like effect. This triggers in the cytoplasmic domain an autophosphorylation reaction on a specific histidine residue, consuming ATP in the process. The activated sensor kinase then transfers the phosphate to a specific aspartic acid of the associated responder (response regulator). The now active response regulator in most cases is able specifically to activate transcription of certain genes in collaboration with RNA polymerase. In a few cases, stimulation of a particular sensor receptor triggers the corresponding response regulator which is specially adapted, not to active RNA polymerase but to bind directly to the motor of the flagellum, thereby controlling the direction of swimming.

Figure 2.

Modular structure of an idealized two component signal transduction system. Incoming signals are picked up by the input domain of the receptor on the cell surface, inducing autophosphorylation in the output domain. A phospho‐relay then propagates a conformational change in the input domain of the responder (response regulator) which finally activates the output domain of the responder. Sensor input domains are highly variable and signal specific. Response regulators, although specifically associating only with their own cognate receptor, are very similar in sequence. The simplest possible relay is portrayed here but some pathways can contain multiple modules of cytoplasmic input–output domains, some fused into a single polypeptide, some separate. TM1 and TM2 and external loop sense and communicate the signal.

Figure 3.

Simplified view of a signalling relay in animal cells. The receptor binds a ligand, a conformational signal is propagated across the membrane bilayer to the cytoplasmic domain and then, according to the type of receptor, several mechanisms of propagating the effect of the signal through the cytoplasm are possible. On the right is illustrated the autophosphorylation of several (e.g. 1, 2, 3) Ser, Thr or Tyr residues stimulated by the binding of a ligand. The activated cytoplasmic domain of the receptor can then in turn activate a specific cytoplasmic protein to trigger a second messenger cascade (Ca2+ or cAMP), modify an ion channel directly, or initiate a phospho‐relay. Other pathways may be triggered by interaction through a G protein. In other variations, illustrated on the left, for some receptors autophosphorylation is sufficient to activate a downstream partner without phospho‐transfer, whilst in yet other cases, the activated receptor acquires and can ‘pass on’ conformational changes without the intervention of phosphorylation. Downstream events in all cases often terminate in an activated transcription factor arriving in the nucleus to control the expression of specific genes.


Further Reading

Bren A and Eisenbach M (2000) How signals are heard during bacterial chemotaxis: protein–protein interactions in sensory signal propagation. Journal of Bacteriology 182: 6865–6873.

Hoch JA and Silhavy TJ (eds) (1995) Two Component Signal Transduction. Washington, USA: ASM Press.

Hossain MZ and Boynton AL (2000) Regulation of Cx43 gap junctions: the gatekeeper and the password. Science, Signal Transduction Knowledge Environment:; 2000/54/pe1.

Jordan JD, Landau EM and Iyengar R (2000) Signaling networks: the origins of cellular multitasking. Cell 103: 193–200.

Lazazzera BA and Grossman AD (1998) The ins and outs of peptide signaling. Trends in Microbiology 6: 288–293.

Matusdaira P, Berk A, Zipursky SL, Baltimore D, Darnell J and Lodish H (2000) Cell‐to‐cell signalling: hormones and receptors. In: Molecular Cell Biology, pp. 849–904. New York: WH Freeman and Co.

Perraud AL, Weiss V and Gross R (1999) Signalling pathways in two‐component phosphorelay systems. Trends in Microbiology 7: 115–120.

Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103: 211–225.

Schwartz MA and Shattil SJ (2000) Signaling networks linking integrins and Rho family GTPases. Trends in Biochemical Sciences 25: 388–391.

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Holland, Katalin A, and Holland, I Barry(Oct 2002) Transmembrane Signalling. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000847]