The Src/Csk regulatory circuit arose early in metazoan evolution.
We have identified a gene encoding a member of the Csk family of non-receptor protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ hybridization analysis of the distribution of RNA from the Hydra Csk gene indicates that it is expressed in most of the epithelial cells of the adult polyp and in gametogenic cells. Comparison of the expression pattern of Hydra Csk with that of STK, the Hydra Src gene orthologue, reveals that the two genes are largely co-expressed. Such co-expression is consistent with a role for Hydra Csk in regulation of STK activity. This possibility was tested directly by coexpressing Hydra Csk with STK in yeast. Co-expression suppressed the growth inhibition seen when STK alone is expressed in yeast. Suppression was dependent on the presence of the putative regulatory tyrosine in the carboxyl-terminal tail of STK. Phosphotyrosine immunoblot analysis confirmed that expression of Csk resulted in suppression of STK kinase activity. Taken together these data indicate that the regulatory circuit involving Src and Csk PTKs was established prior to the divergence of the phylum Cnidaria from the rest of the metazoans.
Miller
M A
MA
Department of Biological Chemistry and The Developmental Biology Center, University of California, Irvine 92697, USA.
Malik
I A
IA
Shenk
M A
MA
Steele
R E
RE
D000818:Animals; D005075:Biological Evolution; D000081247:CSK Tyrosine-Protein Kinase; D020134:Catalytic Domain; D002455:Cell Division / Q000235:genetics; D005786:Gene Expression Regulation; D006829:Hydra / Q000502:physiology*; D010766:Phosphorylation; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D015003:Yeasts / Q000235:genetics / Q000254:growth & development; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases