Possible Clues:

• Southern U.S. hwy.
• Transnational highway built by Ike
• Southernmost cross-country U.S. highway
• The Santa Monica Fwy. is part of it
• Rd. through Mobile and Tucson
• Main lower artery, informally
• FL-to-CA route
• Coast-to-coast U.S. highway
• Calif.-to-Fla. route
• Cross-country route, informally