Receptor tyrosine kinase Heterodimer

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) with pleiotropic developmental functions in metazoans. It is the prototypical member of the ErbB family of RTKs, which can form homodimers or heterodimers with other... 

A well-studied example is provided by the ErbB2 (also called Her or Neu) and EGF receptors, which are receptor tyrosine kinases that form heterodimers with each other and with two other RTKs, ErbB3 and ErbB4, which have various external growth fac-... 

ErbB (or HER in the human). There are four ErbB receptors that form homo- or heterodimers in various combinations upon ligand binding. Specific NRG isoforms preferentially interact with different ErbB dimers. The ErbB receptors are ligand-activated tyrosine kinases structurally similar to the EGF receptor. 

Lenferink, A. E., R. Pinkas Kramarski, M. L. van de Poll, M. J. van Vugt, L. N. Klapper, E. Tzahar, H. Waterman, M. Sela, E. J. van Zoelen, and Y. Yarden. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J. 17 3385-3397.1998. 

The insulin receptor is composed of two heterodimers each heterodimer is composed of an a unit and a P unit. The a unit is extracellular and contains the insulin recognition and binding sites the p unit spans the cellular membrane and contains a tyrosine kinase. Although insulin can bind to a single ap dimer, it binds with higher affinity to the aPaP tetrameric complex. When insulin binds to an a unit, the tyrosine kinase associated with the corresponding p unit is stimulated. Following this, intracellular proteins such as IRS-1 and IRS-2 (IRS=insulin receptor substrate) are phosphorylated by the P subunit tyrosine kinase, and they in turn activate a network of phosphorylations within the receptor cell. 

The insulin receptor is the prototype of a tyrosine kinase receptor with a constitutive oligomeric structure. The signalling form is a a.2/ 2 tetramer, but the unit structure is a heterodimer, consisting of a- and P-subunits. But, in contrast to the homo-and heterodimers of other RTK growth factor receptors, the formation of the insulin receptor oligomer is constitutive and not dependent on ligand binding (see Fig. 1.5). 

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