Eph Receptor Tyrosine Kinases and Their Ligands in Development 153
et al. 1996; Monschau et al. 1997); thus the high degree of promiscuity
in the interaction of ligands and receptors might be limited in vivo.
Binding affinities have often been determined by measuring the
interaction between membrane-bound receptors and (artificially generated) soluble ligands and vice versa. In vivo, Eph ligands are membranebound (being a necessary prerequisite for their function), thus the binding affinities measured possibly do not reflect the real specificity of
interaction. In support of this notion, in some cases high affinity receptor-ligand interactions did not correlate with the induction of a physiological response (e.g., Brambilla et al. 1996).
The level of clustering of Eph ligands, i.e., dimeric vs multimeric
forms, also plays an important role with respect to the mode of intracellular signaling of the corresponding Eph receptors (Stein et al. 1998).
Although dimeric EphrinB2 ligand induced tyrosine phosphorylation of
the corresponding receptor, it did not trigger a physiological response.
In contrast, the tetrameric form of the same ligand led to both receptor
tyrosine phosphorylation and induction of a physiological response in
the receptor-bearing cells. These differences in activity were attributed
to the binding and activation of a low-molecular weight protein tyrosine
phosphatase (LMW-PTP) to the activated receptor complex which is
induced by the tetrameric, but not the dimeric ligand.
In sum, it appears that the functional characterization of this family is
still impeded by our poor understanding of the mode and specificity of
Eph receptor-ligand interactions.
9.3 The Retinotectal Projection
The retinotectal projection is a well-characterized system (Mey and
Thanos 1992; Holt and Harris 1993) for studying the function of the Eph
family, serving as a model for topographic projections which are numerous in the central and peripheral nervous system. In such projections
there is a faithful transfer of spatially organized information from one
area of the brain to another, so that cells neighboring in the projecting
area are connected to cells neighboring in the target area. In the retinotectal projection, temporal retina is connected to rostral tectum and
nasal retina to caudal tectum; similarly, dorsal and ventral retina are
connected to ventral and dorsal tectum, respectively. How such precise
et al. 1996; Monschau et al. 1997); thus the high degree of promiscuity
in the interaction of ligands and receptors might be limited in vivo.
Binding affinities have often been determined by measuring the
interaction between membrane-bound receptors and (artificially generated) soluble ligands and vice versa. In vivo, Eph ligands are membranebound (being a necessary prerequisite for their function), thus the binding affinities measured possibly do not reflect the real specificity of
interaction. In support of this notion, in some cases high affinity receptor-ligand interactions did not correlate with the induction of a physiological response (e.g., Brambilla et al. 1996).
The level of clustering of Eph ligands, i.e., dimeric vs multimeric
forms, also plays an important role with respect to the mode of intracellular signaling of the corresponding Eph receptors (Stein et al. 1998).
Although dimeric EphrinB2 ligand induced tyrosine phosphorylation of
the corresponding receptor, it did not trigger a physiological response.
In contrast, the tetrameric form of the same ligand led to both receptor
tyrosine phosphorylation and induction of a physiological response in
the receptor-bearing cells. These differences in activity were attributed
to the binding and activation of a low-molecular weight protein tyrosine
phosphatase (LMW-PTP) to the activated receptor complex which is
induced by the tetrameric, but not the dimeric ligand.
In sum, it appears that the functional characterization of this family is
still impeded by our poor understanding of the mode and specificity of
Eph receptor-ligand interactions.
9.3 The Retinotectal Projection
The retinotectal projection is a well-characterized system (Mey and
Thanos 1992; Holt and Harris 1993) for studying the function of the Eph
family, serving as a model for topographic projections which are numerous in the central and peripheral nervous system. In such projections
there is a faithful transfer of spatially organized information from one
area of the brain to another, so that cells neighboring in the projecting
area are connected to cells neighboring in the target area. In the retinotectal projection, temporal retina is connected to rostral tectum and
nasal retina to caudal tectum; similarly, dorsal and ventral retina are
connected to ventral and dorsal tectum, respectively. How such precise