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  Topic: immune system evolution, collecting references to recent articles< Next Oldest | Next Newest >  
rafe gutman

Posts: 27
Joined: May 2002

(Permalink) Posted: Dec. 17 2002,18:58   

from the ISCID thread:

martin poenie:  Again Inlay refers to ITAMs in a tunicate gene. This is a reference to a protein called A74 that has no similarity to any other known protein. So what are ITAMs? ITAMs are an arrangement of two tyrosines in a peptide with a certain spacing between them. Tyrosines are widely used in cell signaling. When phosphorylated, they can become ligands for proteins with SH2 domains. What makes ITAMs special is that there are proteins such as ZAP70 that contain dual SH2 domains and bind to the ITAM phosphorylated tyrosines as a unit. At present, no such protein has been identified in tunicates. The ITAM motif is based on four residues. It is possible that these are ordinary SH2 binding sites and that no dual SH2 domain-containing will be found. Until and unless one does find such a protein this is not a compelling argument. If proteins with these dual SH2 domains are found in tunicates, then it becomes a good argument.

rafe:  i'm not an expert on signal transduction, but it seems pretty clear that A74 is involved in immune-related signal transduction, and that tyrosine phosphorylation of the ITAM is part of it. as for the SH2-containing proteins, i should point out that homologues for syk and ZAP70 have been discovered in organisms as distant as hydra [1], and as similar (to tunicates) as sea urchin [2]. additionally, a CD45 homologue, which can augment signaling through ITAMs, was found in hagfish [3]. so while we don't have a tunicate syk-family homologue, many of the other pieces are already in place. it's not unreasonable to think that the downstream targets of A74 will be identified soon, i guess we can reserve judgement til then. do you think it will be homologous to syk/ZAP70?

[1] Steele RE, Stover NA, Sakaguchi M.
Appearance and disappearance of Syk family protein-tyrosine kinase genes during
metazoan evolution.
Gene. 1999 Oct 18;239(1):91-7.

[2] Sakuma M, Onodera H, Suyemitsu T, Yamasu K.
The protein tyrosine kinases of the sea urchin Anthocidaris crassispina.
Zoolog Sci. 1997 Dec;14(6):941-6.

[3]Nagata T, Suzuki T, Ohta Y, Flajnik MF, Kasahara M.
The leukocyte common antigen (CD45) of the Pacific hagfish, Eptatretus stoutii:
implications for the primordial function of CD45.
Immunogenetics. 2002 Jul;54(4):286-91.

i should also note, in reference to dr. poenie's argument, that the genome of a tunicate has been sequenced and dozens of zap-70/syk homologues have been found.  i'm not sure what the best way to search through it is, but i entered "syk" into the search engine for the tunicate genome and found a bunch of hits.  here's one

  23 replies since Dec. 17 2002,18:45 < Next Oldest | Next Newest >  


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