Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity

Oncogene. 1993 Oct;8(10):2879-87.

Abstract

Human cDNA clones encoding four novel putative transmembrane protein serine/threonine kinases, denoted activin receptor-like kinase (ALK) -1, -2, -3 and -4, were obtained using a polymerase chain reaction (PCR)-based strategy. The PCR primers were designed based upon the sequence similarity between the activin receptor type II and Daf-1. The cDNA clones for ALK-1, -2 and -3 encode complete proteins of 503, 509 and 532 amino acids respectively. The ALK-4 cDNA is incomplete and the predicted protein of 383 amino acids has a truncated extracellular domain. The ALKs share similar domain structures, comprising predicted signal sequences at the N-terminals, followed by hydrophilic cysteine-rich ligand-binding domains, single hydrophobic transmembrane regions and C-terminal intracellular portions that consist almost entirely of putative serine/threonine kinase domains. The ALKs have approximately 40% sequence identity to activin receptors type II and IIB, transforming growth factor-beta (TGF-beta) type II receptor and Daf-1 in the kinase domains. However, the sequence identities are higher (60-79%) between ALK-1, -2, -3 and -4, suggesting that they form a subfamily among the putative receptor serine/threonine kinases. The extracellular domains of ALKs show only little sequence identity to other putative receptor serine/threonine kinases, but the cysteine residues are conserved. Their structural properties suggest that ALK-1 to -4 are receptors that may bind ligands that are members of the TGF-beta superfamily. The expression of mRNA in human tissues varied for the different ALKs; ALK-2 and ALK-4 showed ubiquitous tissue expression patterns, whereas the distribution of ALK-1 and ALK-3 varied strongly between different tissues with more restricted expression patterns. These results suggest that each ALK may have different in vivo functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors
  • Amino Acid Sequence
  • Base Sequence
  • Bone Morphogenetic Protein Receptors, Type I
  • Codon / chemistry
  • Codon / genetics
  • Humans
  • Molecular Sequence Data
  • Open Reading Frames
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / isolation & purification*
  • RNA, Messenger / genetics
  • RNA, Messenger / isolation & purification
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / isolation & purification*
  • Sequence Analysis, DNA

Substances

  • Codon
  • RNA, Messenger
  • Receptors, Cell Surface
  • Protein-Serine-Threonine Kinases
  • Activin Receptors
  • BMPR1A protein, human
  • Bone Morphogenetic Protein Receptors, Type I

Associated data

  • GENBANK/Z22533
  • GENBANK/Z22534
  • GENBANK/Z22535
  • GENBANK/Z22536