The protein kinases of Caenorhabditis elegans : A model for signal transduction in multicellular organisms

The protein kinases of Caenorhabditis elegans: A model for signal transduction in multicellular organisms

^†The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037; and ^*SUGEN, 230 East Grand Avenue, South San Francisco, CA 94080

Contributed by Tony Hunter

Abstract

Caenorhabditis elegans should soon be the first multicellular organism whose complete genomic sequence has been determined. This achievement provides a unique opportunity for a comprehensive assessment of the signal transduction molecules required for the existence of a multicellular animal. Although the worm C. elegans may not much resemble humans, the molecules that regulate signal transduction in these two organisms prove to be quite similar. We focus here on the content and diversity of protein kinases present in worms, together with an assessment of other classes of proteins that regulate protein phosphorylation. By systematic analysis of the 19,099 predicted C. elegans proteins, and thorough analysis of the finished and unfinished genomic sequences, we have identified 411 full length protein kinases and 21 partial kinase fragments. We also describe 82 additional proteins that are predicted to be structurally similar to conventional protein kinases even though they share minimal primary sequence identity. Finally, the richness of phosphorylation-dependent signaling pathways in worms is further supported with the identification of 185 protein phosphatases and 128 phosphoprotein-binding domains (SH2, PTB, STYX, SBF, 14-3-3, FHA, and WW) in the worm genome.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: hunter{at}salk.edu.
This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in April 28, 1998.
Abbreviations:

PKA,

protein kinase A;

MAPK,

mitogen-activated protein kinase;

CDK,

cyclin-dependent kinase;

PTK,

protein-tyrosine kinase;

RTK,

receptor protein-tyrosine kinases;

CTK,

cytoplasmic protein-tyrosine kinases;

STAT,

signal transducer and activator of transcription;

IRS,

insulin receptor substrate;

NLK,

NEMO-like kinase;

APH,

aminoglycoside phosphotransferases;

PTP,

protein-tyrosine phosphatase