Background: DDR1 is a constitutively dimeric receptor tyrosine kinase that is activated by collagen. The mechanism of transmembrane signaling is unknown.Results: DDR1 activation is unaffected by disulfide cross-links, insertions, or deletions in the extracellular juxtamembrane region.Conclusion: The extracellular juxtamembrane region of DDR1 does not transmit a conformational change across the cell membrane.Significance: The activation mechanism of DDR1 appears to be unique among receptor tyrosine kinases.