Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity.
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.
Ludwig Institute for Cancer Research, Uppsala, Sweden.
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P
ten Dijke
H
H
Ichijo
P
P
Franzén
P
P
Schulz
J
J
Saras
H
H
Toyoshima
C H
CH
Heldin
K
K
Miyazono
D029404:Activin Receptors; D000595:Amino Acid Sequence; D001483:Base Sequence; D052005:Bone Morphogenetic Protein Receptors, Type I; D003062:Codon / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification*; D017422:Sequence Analysis, DNA
D003062:Codon; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I