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N. Holder et al.
EphB2 and they potentially link signalling to control of cytoskeletal
dynamics (Holland et al. 1997; Bruckner and Klein 1998).
C-terminal to the kinase domain, a conserved region of 60-70 amino
acids is present in all Eph receptors and was identified as a sterile alpha
motif (SAM) domain (Schultz et al. 1997). An invariant tyrosine located
within the SAM domain of EphB 1 is required for binding of the Grb 1 0
adaptor protein (Stein et al. 1996). It is of interest that GrblO shares
homology with a Caenorhabditis elegans gene product thought to be
involved in neural cell migration (Ooi et al. 1995). The tyrosine within
the SAM domain of EphB 1 is also required for binding of a low
molecular weight phosphotyrosine phosphatase (LMW-PTP) whose recruitment correlates with functional responses such as endothelial capillary-like assembly and cell attachment after stimulation with higher
order ephrin clusters (Stein et al. 1998).
.
Finally, a PDZ-binding motif which interacts with PDZ domain
proteins is present at the C-terminal tail of Eph receptors (PDZ for
postsynaptic density protein, discs large, zona occludens; Sheng 1996).
In line with their known interactions with synaptic membrane proteins,
PDZ domain proteins were found to cluster and co-localize with Eph
receptors at synapses of cultured hippocampal neurons (Torres et al.
1998). Some PDZ domain proteins become tyrosine phosphorylated
when complexed with Eph receptors (Torres et al. 1998) and an intact
Eph kinase domain appears to be required for the interaction (Hock et al.
1998). Interestingly, a functional PDZ-binding motif is also present at
the C-terminus of transmembrane ephrin-B proteins (Torres et al. 1998).
PDZ domain proteins may therefore be important mediators of ephrin
clustering and/or signalling.
8.6 Conclusions
Eph receptors and ephrins are dynamically expressed during development of a range of vertebrate species and have been isolated in C.
elegans (George et al. 1998). In this review I have outlined the role that
Eph/ephrin signalling plays in axon guidance, neural crest migration
and segmentation to illustrate the importance of these signalling proteins to fundamental morphogenetic mechanisms in the embryo. The
examples are principally chosen from development of the nervous sys-
N. Holder et al.
EphB2 and they potentially link signalling to control of cytoskeletal
dynamics (Holland et al. 1997; Bruckner and Klein 1998).
C-terminal to the kinase domain, a conserved region of 60-70 amino
acids is present in all Eph receptors and was identified as a sterile alpha
motif (SAM) domain (Schultz et al. 1997). An invariant tyrosine located
within the SAM domain of EphB 1 is required for binding of the Grb 1 0
adaptor protein (Stein et al. 1996). It is of interest that GrblO shares
homology with a Caenorhabditis elegans gene product thought to be
involved in neural cell migration (Ooi et al. 1995). The tyrosine within
the SAM domain of EphB 1 is also required for binding of a low
molecular weight phosphotyrosine phosphatase (LMW-PTP) whose recruitment correlates with functional responses such as endothelial capillary-like assembly and cell attachment after stimulation with higher
order ephrin clusters (Stein et al. 1998).
.
Finally, a PDZ-binding motif which interacts with PDZ domain
proteins is present at the C-terminal tail of Eph receptors (PDZ for
postsynaptic density protein, discs large, zona occludens; Sheng 1996).
In line with their known interactions with synaptic membrane proteins,
PDZ domain proteins were found to cluster and co-localize with Eph
receptors at synapses of cultured hippocampal neurons (Torres et al.
1998). Some PDZ domain proteins become tyrosine phosphorylated
when complexed with Eph receptors (Torres et al. 1998) and an intact
Eph kinase domain appears to be required for the interaction (Hock et al.
1998). Interestingly, a functional PDZ-binding motif is also present at
the C-terminus of transmembrane ephrin-B proteins (Torres et al. 1998).
PDZ domain proteins may therefore be important mediators of ephrin
clustering and/or signalling.
8.6 Conclusions
Eph receptors and ephrins are dynamically expressed during development of a range of vertebrate species and have been isolated in C.
elegans (George et al. 1998). In this review I have outlined the role that
Eph/ephrin signalling plays in axon guidance, neural crest migration
and segmentation to illustrate the importance of these signalling proteins to fundamental morphogenetic mechanisms in the embryo. The
examples are principally chosen from development of the nervous sys-