SEL-5, A Serine/Threonine Kinase That Facilitates lin-12 Activity in Caenorhabditis elegans

SEL-5, A Serine/Threonine Kinase That Facilitates lin-12 Activity in Caenorhabditis elegans

Hanna Fares^a and Iva Greenwald^a
^a Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York 10032

Corresponding author: Iva Greenwald, 701 West 168th St., HHSC Rm. 720, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032., greenwald{at}cuccfa.ccc.columbia.edu (E-mail)

Communicating editor: R. K. HERMAN

Ligands present on neighboring cells activate receptors of theLIN-12/Notch family by inducing a proteolytic cleavage eventthat releases the intracellular domain. Mutations that appearto eliminate sel-5 activity are able to suppress constitutiveactivity of lin-12(d) mutations that are point mutations inthe extracellular domain of LIN-12, but cannot suppress lin-12(intra),the untethered intracellular domain. These results suggest thatsel-5 acts prior to or during ligand-dependent release of theintracellular domain. In addition, sel-5 suppression of lin-12(d)mutations is tissue specific: loss of sel-5 activity can suppressdefects in the anchor cell/ventral uterine precursor cell fatedecision and a sex myoblast/coelomocyte decision, but cannotsuppress defects in two different ventral hypodermal cell fatedecisions in hermaphrodites and males. sel-5 encodes at leasttwo proteins, from alternatively spliced mRNAs, that share anamino-terminal region and differ in the carboxy-terminal region.The amino-terminal region contains the hallmarks of a serine/threoninekinase domain, which is most similar to mammalian GAK1 and yeastPak1p.

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